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1. Hybrid Localized SOI/Bulk technology for Low Power System-on-Chip.

Author: Beijing Meteorological Bureau ; Beijing Meteorological Bureau, STMicroelectronics [Crolles] (ST-CROLLES) ; STMicroelectronics, Laboratoire de physiopathologie de la nutrition (LPN) ; CNRS - Université Paris VII - Paris Diderot, Université Paris-Sud (IDES) ; CNRS, Science et Ingénierie des Matériaux et Procédés (SIMaP) ; Université Joseph Fourier - Grenoble I - Institut National Polytechnique de Grenoble (INPG) - CNRS, Laboratoire d'Electronique et des Technologies de l'Information (LETI) ; CEA, Institut de Microélectronique, Electromagnétisme et Photonique - Laboratoire d'Hyperfréquences et Caractérisation (IMEP-LAHC) ; Université de Savoie - Université Joseph Fourier - Grenoble I - Institut National Polytechnique de Grenoble (INPG) - CNRS, Huguenin, J.-L., Monfray, S., Bidal, G., Denorme, S., Perreau, P., Barnola, S., Samson, M.-P., Arvet, C., Benotmane, K., Loubet, N., Liu, Q., Campidelli, Y., Leverd, F., Abbate, F., Clement, L., Borowiak, C., Cros, A., Bajolet, A., Handler, S., Marin-Cudraz, D., Benoist, T., Galy, P., Fenouillet-Beranger, C., Faynot, O., Ghibaudo, G., Boeuf, F., Skotnicki, T., Beijing Meteorological Bureau ; Beijing Meteorological Bureau, STMicroelectronics [Crolles] (ST-CROLLES) ; STMicroelectronics, Laboratoire de physiopathologie de la nutrition (LPN) ; CNRS - Université Paris VII - Paris Diderot, Université Paris-Sud (IDES) ; CNRS, Science et Ingénierie des Matériaux et Procédés (SIMaP) ; Université Joseph Fourier - Grenoble I - Institut National Polytechnique de Grenoble (INPG) - CNRS, Laboratoire d'Electronique et des Technologies de l'Information (LETI) ; CEA, Institut de Microélectronique, Electromagnétisme et Photonique - Laboratoire d'Hyperfréquences et Caractérisation (IMEP-LAHC) ; Université de Savoie - Université Joseph Fourier - Grenoble I - Institut National Polytechnique de Grenoble (INPG) - CNRS, Huguenin, J.-L., Monfray, S., Bidal, G., Denorme, S., Perreau, P., Barnola, S., Samson, M.-P., Arvet, C., Benotmane, K., Loubet, N., Liu, Q., Campidelli, Y., Leverd, F., Abbate, F., Clement, L., Borowiak, C., Cros, A., Bajolet, A., Handler, S., Marin-Cudraz, D., Benoist, T., Galy, P., Fenouillet-Beranger, C., Faynot, O., Ghibaudo, G., Boeuf, F., and Skotnicki, T.
Abstract: International audience

2. P239 Une brève augmentation des acides gras libres en direction du cerveau diminue la prise alimentaire, chez le rat

Author: Christophe Guissard, Christophe Magnan, Nicolas Marsollier, Luc Pénicaud, Céline Cruciani-Guglielmacci, Anne Lorsignol, Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Métabolisme Plasticité et Mitochondrie [lié à l'ex IFR 31] (LMPM), IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), ALFEDIAM, Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiopathologie de la nutrition ( LPN ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Métabolisme, plasticité et mitochondrie, Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR31-Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), and Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS )
Subjects: 2. Zero hunger, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, Diabetes and Metabolism, Internal Medicine, 030209 endocrinology & metabolism, General Medicine, 030204 cardiovascular system & hematology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Introduction Il est bien etabli que le systeme nerveux central controle l'homeostasie energetique via l'utilisation des nutriments et l'ajustement de la prise alimentaire ; en retour les nutriments exercent un retrocontrole en modulant les activites neuronales, le « nutrient sensing ». Le but de cette etude etait d'etablir quel nutriment est le principal responsable de l'effet satietogene d'un repas de part une action directe sur le cerveau. Materiels et methodes Plusieurs groupes de rats Wistar mâles ont ete prives de nourriture pendant 5 heures, puis perfuses dans l'artere carotide en direction du cerveau pendant 10 minutes avec du glucose 20 %, une emulsion de triglycerides (Intralipid ® , IL) ou une emulsion d'acides amines, a un debit ne modifiant pas les concentrations circulantes en nutriments. A la fin de la perfusion, les animaux ont ete renourris et la prise alimentaire suivie pendant 5 heures. Des rats ont egalement ete perfuses de lipides plus etomoxir, un inhibiteur de la β oxydation. Resultats La perfusion de glucose, d'acides amines ou de triglycerides ne modifie pas la prise alimentaire, en revanche les triglycerides associes a l'heparine (qui stimule leur hydrolyse) ont conduit a une nette diminution de la prise alimentaire, ce qui indique que les AGL sont vraisemblablement les principaux acteurs du « lipid sensing ». Le marquage c-fos a permis de mettre en evidence que la perfusion IL/heparine a provoque une augmentation de l'activation neuronale dans le noyau arque, l'hypothalamus ventromedian et le noyau paraventriculaire, ce qui est caracteristique d'une reponse anorexigene. Enfin, il s'est avere que l'etomoxir seul suffit a baisser la prise alimentaire, tandis que le groupe IL/heparine/etomoxir presente une prise alimentaire similaire aux rats IL/heparine. Ces resultats suggerent fortement que c'est l'accumulation des acyls-CoA a l'interieur des neurones, et non leur oxydation, qui est a l'origine du signal de satiete. Conclusion Nous pouvons conclure que les AGL ont la capacite de moduler la prise alimentaire par un effet direct sur les neurones hypothalamiques, vraisemblablement via une augmentation des acyls-CoA.
Published: 2009

3. Mitochondrial reactive oxygen species are obligatory signals for glucose-induced insulin secretion

Author: Melis Karaca, Julien Castel, Luc Pénicaud, Christophe Magnan, Lionel Carneiro, Corinne Leloup, Anne-Laure Colombani, Louis Casteilla, Alain Ktorza, Cécile Tourrel-Cuzin, Delon, Viviane, Développement et Communication Chimique chez les Insectes ( DCCI ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire de physiopathologie de la nutrition ( LPN ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de recherche sur les Ions, les MAtériaux et la Photonique ( CIMAP - UMR 6252 ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ), Neurobiologie, plasticité tissulaire et métabolisme énergétique ( NPTME ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Développement et Communication Chimique chez les Insectes (DCCI), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)
Subjects: Male, Mitochondrial ROS, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, chemistry.chemical_element, Calcium, Mitochondrion, Biology, Superoxide dismutase, Islets of Langerhans, 03 medical and health sciences, chemistry.chemical_compound, Adenosine Triphosphate, 0302 clinical medicine, Superoxides, Internal medicine, Insulin Secretion, Internal Medicine, medicine, Animals, Insulin, Secretion, Chromans, Rats, Wistar, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, Superoxide Dismutase, Superoxide, NAD, Mitochondria, Rats, Kinetics, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Glucose, Endocrinology, Islet Studies, chemistry, biology.protein, Thapsigargin, Reactive Oxygen Species, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Signal Transduction
Abstract: OBJECTIVE—Insulin secretion involves complex events in which the mitochondria play a pivotal role in the generation of signals that couple glucose detection to insulin secretion. Studies on the mitochondrial generation of reactive oxygen species (ROS) generally focus on chronic nutrient exposure. Here, we investigate whether transient mitochondrial ROS production linked to glucose-induced increased respiration might act as a signal for monitoring insulin secretion. RESEARCH DESIGN AND METHODS—ROS production in response to glucose was investigated in freshly isolated rat islets. ROS effects were studied using a pharmacological approach and calcium imaging. RESULTS—Transient glucose increase from 5.5 to 16.7 mmol/l stimulated ROS generation, which was reversed by antioxidants. Insulin secretion was dose dependently blunted by antioxidants and highly correlated with ROS levels. The incapacity of β-cells to secrete insulin in response to glucose with antioxidants was associated with a decrease in ROS production and in contrast to the maintenance of high levels of ATP and NADH. Then, we investigated the mitochondrial origin of ROS (mROS) as the triggering signal. Insulin release was mimicked by the mitochondrial-complex blockers, antimycin and rotenone, that generate mROS. The adding of antioxidants to mitochondrial blockers or to glucose was used to lower mROS reversed insulin secretion. Finally, calcium imaging on perifused islets using glucose stimulation or mitochondrial blockers revealed that calcium mobilization was completely reversed using the antioxidant trolox and that it was of extracellular origin. No toxic effects were present using these pharmacological approaches. CONCLUSIONS—Altogether, these complementary results demonstrate that mROS production is a necessary stimulus for glucose-induced insulin secretion.
Published: 2009

4. Increased pancreatic islet blood flow in 48-hour glucose-infused rats: involvement of central and autonomic nervous systems

Author: Atef, N., Laury, M. C., N'Guyen, J.M., Ktorza, Alain, Pénicaud, Luc, Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiopathologie de la nutrition ( LPN ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), and Delon, Viviane
Subjects: [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 1997

5. Cellular changes during cold acclimatation in adipose tissues

Author: Cousin, Béatrice, Bascands-Viguerie, N., Kassis, N., Nibbelink, M., Ambid, L., Casteilla, Louis, Pénicaud, Luc, Science et Ingénierie des Matériaux et Procédés (SIMaP), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire de physiopathologie de la nutrition (LPN), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Science et Ingénierie des Matériaux et Procédés ( SIMaP ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Laboratoire de physiopathologie de la nutrition ( LPN ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Neurobiologie, plasticité tissulaire et métabolisme énergétique ( NPTME ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), and Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS )
Subjects: [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 1996

6. Effect of S-21663 (PMS 812), an imidazoline derivative, on glucose tolerance and insulin secretion in a rat model of type II diabetes

Author: Wang, X., Rondu, F., Lamouri, A., Dokhan, R., Marc, S., Touboul, E., Pfeiffer, B., Manechez, D., Renard, P., Guardiola-Lemaitre, B., Godfroid, J. J., Ktorza, Alain, Pénicaud, Luc, CAN-FOR, National Institute of Advanced Science and Technology, Institut de recherches Servier (INSTITUT DE RECHERCHES SERVIER), INSTITUT SERVIER, Laboratoire de physiopathologie de la nutrition (LPN), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de recherches Servier ( INSTITUT DE RECHERCHES SERVIER ), Laboratoire de physiopathologie de la nutrition ( LPN ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), and Delon, Viviane
Subjects: Male, Dose-Response Relationship, Drug, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Imidazoles, Glucose Tolerance Test, Diabetes Mellitus, Experimental, Rats, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Disease Models, Animal, Animals, Insulin, Rats, Wistar, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; We have studied the activity of S-21663 (PMS 812), a new imidazoline derivative, in a rat model of Type II diabetes obtained by i.v. injection of a low dose (35 mg/kg) of streptozotocin, using glucose tolerance tests. Glucose tolerance and insulin secretion were measured as the delta G and the delta l, i.e., the respective increase in glycemia and insulinemia over 30 min after the glucose load. The rate of glucose disappearance was calculated as the K coefficient and the insulin response to glucose as the delta l/delta G. After i.p. injection of S-21663, delta G (millimoles per liter per minute) was decreased (71.7 +/- 10.1 vs. 112.6 +/- 15.1; P < .05), whereas K was increased (3.3 +/- 0.3 vs. 1.5 +/- 0.1; P < .05). Insulin secretion was also largely improved (delta l/delta G: 90.9 +/- 22.2 vs. 18.3 +/- 2.6; P < .05). Oral administration of the product was almost as efficient as i.p. injection. Chronic treatment (15 days) increased the efficiency. Insulin secretion measured in vitro at both 2.8 and 16.6 mM glucose was quadrupled by S-21663 (100 microM). S-21663 binds neither to alpha-2 adrenoceptors nor to known imidazoline binding sites. S-21663 can be considered as a potential hypoglycemic agent in Type II diabetes.
Published: 1996

7. Dairy consumption is associated with lower plasma dihydroceramides in women from the D.E.S.I.R. cohort

Author: A. Nicolas, B. Balkau, Ronan Roussel, Leonore Wigger, Soraya Fellahi, Michel Marre, Jean-Philippe Bastard, Céline Cruciani-Guglielmacci, Christophe Magnan, Gilberto Velho, Mark Ibberson, Frédéric Fumeron, H. Le Stunff, Laboratoire Kastler Brossel (LKB (Jussieu)), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Plastics and Rubber Engineering Department, Algerian Petroleum Institute, 35000 Boumerdes, Algeria, Algerian Petroleum Institute, Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Pathologie métabolique et hormonale du développement, Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - CHU Bichat, University of Versailles St.-Quentin, UMRS 1018, Villejuif, Fumeron, Frédéric, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Center for Integrated Genomics, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'endocrinologie, diabétologie et nutrition [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), This research was supported by grants from CNIEL (National Interprofessional Center for theDairy Economy) and IMIDIA (Innovative Medicines Initiative Joint Undertaking) (grantagreement no. 155005).The D.E.S.I.R. study has been funded by INSERM contracts with Caisse nationale del'assurance Maladie des Travailleurs Salariés (CNAMTS), Lilly, Novartis Pharma, andSanofi-Aventis, INSERM (Réseaux en Santé Publique, Interactions entre les déterminants dela santé, Cohortes Santé TGIR 2008), the Association Diabète Risque Vasculaire, theFédération Française de Cardiologie, La Fondation de France, Association de LangueFrançaise pour l'Etude du Diabète et des Maladies Métaboliques (ALFEDIAM)/SociétéFrancophone de Diabétologie (SFD), l'Office National Interprofessionnel des Vins (ONIVINS), Ardix Medical, Bayer Diagnostics, Becton Dickinson, Cardionics, Merck Santé, Novo Nordisk, Pierre Fabre, Roche, Topcon, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Lausanne (UNIL), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Adult, Longitudinal study, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, Type 2 diabetes, Ceramides, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Animal science, Diabetes mellitus, Internal Medicine, Medicine, Humans, Longitudinal Studies, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Aged, 2. Zero hunger, Consumption (economics), 0303 health sciences, Total plasma, business.industry, Incidence, Confounding, General Medicine, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Diet, Lower incidence, [SDV] Life Sciences [q-bio], [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Diabetes Mellitus, Type 2, Cohort, Female, Dairy Products, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Aim In the D.E.S.I.R. cohort, higher consumption of dairy products was associated with lower incidence of hyperglycaemia, and dihydroceramide concentrations were higher in those who progressed to diabetes. Our aim here was to study the relationships between dairy consumption and concentrations of dihydroceramides and ceramides. Methods In the D.E.S.I.R. cohort, men and women aged 30–65 years, volunteers from West-Central France, were included in a 9-year follow-up with examinations every 3 years, including food-frequency questionnaires. Two items concerned dairy products (cheese, other dairy products except cheese). At each examination, dihydroceramides and ceramides were determined by mass spectrometry in a cohort subset; in the present study, the 105 people who did not progress to type 2 diabetes were analyzed, as the disorder per se might be a confounding factor. Results Higher consumption of dairy products (except cheese) was associated with total plasma dihydroceramides during the follow-up, but only in women (P = 0.01 for gender interaction). In fact, dihydroceramide levels were lower in women with high vs low consumption (P = 0.03), and were significantly increased during follow-up (P = 0.01) in low consumers only. There was also a trend for lower ceramides in women with high dairy (except cheese) intakes (P = 0.08). Cheese was associated with dihydroceramide and ceramide changes during follow-up (P = 0.04 for both), but no clear trend was evident in either low or high consumers. Conclusion These results show that, in women, there is an inverse association between fresh dairy product consumption and predictive markers (dihydroceramides) of type 2 diabetes.
Published: 2019
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8. Mitochondrial Dynamin-Related Protein 1 (DRP1) translocation in response to cerebral glucose is impaired in a rat model of early alteration in hypothalamic glucose sensing

Author: Sylvie Grall, Claire Fenech, Chloé Chrétien, Lucie Desmoulins, Claude Knauf, Xavier Fioramonti, Anne Galinier, Christophe Magnan, Lionel Carneiro, Luc Pénicaud, Camille Allard, Audren Fournel, Stephan Collins, Corinne Leloup, Thomas Mouillot, Romain Paccoud, Fabienne Liénard, Céline Cruciani-Guglielmacci, Aurore Quinault, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), STROMALab, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine [Rangueil], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Laboratoire de physiopathologie de la nutrition (LPN), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Développement et Communication Chimique chez les Insectes (DCCI), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Unité de Biologie Fonctionnelle et Adaptative [Avant 2020] (BFA (UMR_8251 / U1133)), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by a PhD fellowship from the Ministere de l'Enseignement Superieur et de la Recherche to LD and grants to CL: Institut de France (NRJ award), Agence National de la Recherche No ANR-11-BSV1-0007, recurrent financial supports from the Burgundy's Regional Council, the University of Burgundy and the CNRS. CCG and CM received grant from the Agence Nationale de la Recherche No ANR-16-CE14-0026., Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de Recherche en Santé Digestive (IRSD ), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Pénicaud, Luc
Subjects: 0301 basic medicine, Blood Glucose, Male, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Mitochondrion, Energy homeostasis, DNM1L, 0302 clinical medicine, AMP-Activated Protein Kinase Kinases, Insulin-Secreting Cells, Insulin Secretion, Premovement neuronal activity, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, chemistry.chemical_classification, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Chemistry, Mitochondrial fission, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Mitochondria, [SDV] Life Sciences [q-bio], Protein Transport, Carotid Arteries, Hypothalamus, Glucose sensing, Original Article, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Signal Transduction, Dynamins, medicine.medical_specialty, endocrine system, lcsh:Internal medicine, Sensory Receptor Cells, 030209 endocrinology & metabolism, DRP1, 03 medical and health sciences, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Rats, Wistar, lcsh:RC31-1245, Molecular Biology, Reactive oxygen species, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, AMPK, Cell Biology, Rats, ROS signaling, 030104 developmental biology, Endocrinology, Reactive Oxygen Species, Protein Kinases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objective Hypothalamic glucose sensing (HGS) initiates insulin secretion (IS) via a vagal control, participating in energy homeostasis. This requires mitochondrial reactive oxygen species (mROS) signaling, dependent on mitochondrial fission, as shown by invalidation of the hypothalamic DRP1 protein. Here, our objectives were to determine whether a model with a HGS defect induced by a short, high fat-high sucrose (HFHS) diet in rats affected the fission machinery and mROS signaling within the mediobasal hypothalamus (MBH). Methods Rats fed a HFHS diet for 3 weeks were compared with animals fed a normal chow. Both in vitro (calcium imaging) and in vivo (vagal nerve activity recordings) experiments to measure the electrical activity of isolated MBH gluco-sensitive neurons in response to increased glucose level were performed. In parallel, insulin secretion to a direct glucose stimulus in isolated islets vs. insulin secretion resulting from brain glucose stimulation was evaluated. Intra-carotid glucose load-induced hypothalamic DRP1 translocation to mitochondria and mROS (H2O2) production were assessed in both groups. Finally, compound C was intracerebroventricularly injected to block the proposed AMPK-inhibited DRP1 translocation in the MBH to reverse the phenotype of HFHS fed animals. Results Rats fed a HFHS diet displayed a decreased HGS-induced IS. Responses of MBH neurons to glucose exhibited an alteration of their electrical activity, whereas glucose-induced insulin secretion in isolated islets was not affected. These MBH defects correlated with a decreased ROS signaling and glucose-induced translocation of the fission protein DRP1, as the vagal activity was altered. AMPK-induced inhibition of DRP1 translocation increased in this model, but its reversal through the injection of the compound C, an AMPK inhibitor, failed to restore HGS-induced IS. Conclusions A hypothalamic alteration of DRP1-induced fission and mROS signaling in response to glucose was observed in HGS-induced IS of rats exposed to a 3 week HFHS diet. Early hypothalamic modifications of the neuronal activity could participate in a primary defect of the control of IS and ultimately, the development of diabetes., Graphical abstract Image 1, Highlights • Only three weeks of HFHS diet consumption impairs hypothalamic glucose sensing. • HFHS consumption alters central glucose-induced vagal control of insulin secretion. • Glucose-induced ROS production and mitochondrial fission are decreased in HFHS rats. • Impaired translocation of DRP1in HFHS rats does not involve its phosphorylation.
Published: 2019
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9. Adipocyte Glucocorticoid Receptor Deficiency Promotes Adipose Tissue Expandability and Improves the Metabolic Profile Under Corticosterone Exposure

Author: Marie Garcia, M. Buyse, Marthe Moldes, Raphaël George Denis, Héloïse Dalle, Bénédicte Antoine, V. Boehm, Christophe Magnan, Thi Thu Huong Do, Antonin Lamaziere, Serge Luquet, Tatiana Ledent, Catherine Postic, Bruno Fève, Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Pharmacie [CHU Saint Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire de physiopathologie de la nutrition (LPN), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Endocrinologie, Diabétologie et d'Endocrinologie de la Reproduction [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Endocrinologie, diabétologie et endocrinologie de la reproduction [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Luquet, Serge
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, [SDV.BA] Life Sciences [q-bio]/Animal biology, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Macrophage polarization, Adipose tissue, 030209 endocrinology & metabolism, Mice, 03 medical and health sciences, chemistry.chemical_compound, Receptors, Glucocorticoid, 0302 clinical medicine, Glucocorticoid receptor, Corticosterone, Internal medicine, Adipocyte, Adipocytes, Internal Medicine, medicine, Animals, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Mice, Knockout, Glucose tolerance test, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, [SDV.BA]Life Sciences [q-bio]/Animal biology, Lipid metabolism, Glucose Tolerance Test, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Flow Cytometry, medicine.disease, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Adipose Tissue, chemistry, Lipodystrophy, Metabolism, Inborn Errors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Widely used for their anti-inflammatory and immunosuppressive properties, glucocorticoids are nonetheless responsible for the development of diabetes and lipodystrophy. Despite an increasing number of studies focused on the adipocyte glucocorticoid receptor (GR), its precise role in the molecular mechanisms of these complications has not been elucidated. In keeping with this goal, we generated a conditional adipocyte-specific murine model of GR invalidation (AdipoGR knockout [KO] mice). Interestingly, when administered a corticosterone treatment to mimic hypercorticism conditions, AdipoGR-KO mice exhibited an improved glucose tolerance and insulin sensitivity. This was related to the adipose-specific activation of the insulin-signaling pathway, which contributed to fat mass expansion, as well as a shift toward an anti-inflammatory macrophage polarization in adipose tissue of AdipoGR-KO animals. Moreover, these mice were protected against ectopic lipid accumulation in the liver and displayed an improved lipid profile, contributing to their overall healthier phenotype. Altogether, our results indicate that adipocyte GR is a key factor of adipose tissue expansion and glucose and lipid metabolism control, which should be taken into account in the further design of adipocyte GR-selective modulators.
Published: 2019
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10. correction : Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity

Author: Bravo-San Pedro, José, Sica, Valentina, Martins, Isabelle, Pol, Jonathan, Loos, Friedemann, Maiuri, Maria Chiara, Durand, Sylvère, Bossut, Noélie, Aprahamian, Fanny, Anagnostopoulos, Gerasimos, Niso-Santano, Mireia, Aranda, Fernando, Ramírez-Pardo, Ignacio, Lallement, Justine, Denom, Jessica, Boedec, Erwan, Gorwood, Philip, Ramoz, Nicolas, Clement, Karine, Pelloux, Véronique, Rohia, Alili, Pattou, François, Raverdy, Violeta, Caiazzo, Robert, Denis, Raphaël, Boya, Patricia, Galluzzi, Lorenzo, Madeo, Frank, Migrenne-Li, Stéphanie, Cruciani-Guglielmacci, Céline, Tavernarakis, Nektarios, López-Otín, Carlos, Magnan, Christophe, Kroemer, Guido, POL, Jonathan, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), Apoptose, cancer et immunité (Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centro de Investigaciones Biológicas (CSIC), Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB), Karl-Franzens-Universität Graz, Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology, Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo [Oviedo]-Instituto Universitario de Oncología, Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP), Karolinska University Hospital [Stockholm], Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Équipe NutriOmics [Paris], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universidad de Oviedo-Instituto Universitario de Oncología, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École Pratique des Hautes Études (EPHE), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), and Centre de Psychiatrie et Neurosciences (U894)
Subjects: [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: International audience; Refers toJosé M. Bravo-San Pedro, Valentina Sica, Isabelle Martins, Jonathan Pol, Friedemann Loos, Maria Chiara Maiuri, Sylvère Durand, Noélie Bossut, Fanny Aprahamian, Gerasimos Anagnostopoulos, Mireia Niso-Santano, Fernando Aranda, Ignacio Ramírez-Pardo, Justine Lallement, Jessica Denom, Erwan Boedec, Philip Gorwood, Nicolas Ramoz, Karine Clément, Veronique Pelloux, Alili Rohia, François Pattou, Violeta Raverdy, Robert Caiazzo, Raphaël G.P. Denis, Patricia Boya, Lorenzo Galluzzi, Frank Madeo, Stéphanie Migrenne-Li, Céline Cruciani-Guglielmacci, Nektarios Tavernarakis, Carlos López-Otín, Christophe Magnan, Guido KroemerAcyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and ObesityCell Metabolism, Volume 30, Issue 4, 1 October 2019, Pages 754-767.e9
Published: 2019
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11. Protective role of the ELOVL2/docosahexaenoic acid axis in glucolipotoxicity-induced apoptosis in rodent beta cells and human islets

Author: Hervé Le Stunff, Kelly Meneyrol, Nadim Kassis, Mark Ibberson, Julien Véret, Christophe Magnan, Lara Bellini, Isabelle Hainault, Jessica Denom, Céline Cruciani-Guglielmacci, Véronique Lenoir, Piero Marchetti, Agnieszka Blachnio-Zabielska, Mélanie Campana, Marta Chacinska, Carina Prip-Buus, Marco Bugliani, Bernard Thorens, Claude Rouch, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Clinical and Experimental Medicine [Pisa, Italy], University of Pisa [Italy], Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), FACULTAD DE CIENCIAS Y FILOSOFIA, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Medical University of Bialystok, Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Laboratoire de physiopathologie de la nutrition (LPN), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), SIB Swiss Institute of Bioinformatics, and Université de Lausanne
Subjects: AMPK, 0301 basic medicine, medicine.medical_specialty, Ceramide, Docosahexaenoic Acids, Fatty Acid Elongases, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Palmitates, Apoptosis, 030209 endocrinology & metabolism, Pancreatic beta cells, Islets of Langerhans, Mice, 03 medical and health sciences, chemistry.chemical_compound, Endocrinology, 0302 clinical medicine, Carnitine palmitoyltransferase 1, Downregulation and upregulation, ELOVL2, Acetyltransferases, Insulin-Secreting Cells, Internal medicine, Internal Medicine, medicine, Animals, Glucose homeostasis, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, food and beverages, Fatty acid, Type 2 diabetes, DHA, Glucolipotoxicity, Diabetes and Metabolism, Mitochondrial β-oxidation, Glucose, 030104 developmental biology, chemistry, Docosahexaenoic acid, Beta cell, Oxidation-Reduction, Etomoxir
Abstract: Dietary n-3 polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), are known to influence glucose homeostasis. We recently showed that Elovl2 expression in beta cells, which regulates synthesis of endogenous DHA, was associated with glucose tolerance and played a key role in insulin secretion. The present study aimed to examine the role of the very long chain fatty acid elongase 2 (ELOVL2)/DHA axis on the adverse effects of palmitate with high glucose, a condition defined as glucolipotoxicity, on beta cells. We detected ELOVL2 in INS-1 beta cells and mouse and human islets using quantitative PCR and western blotting. Downregulation and adenoviral overexpression of Elovl2 was carried out in beta cells. Ceramide and diacylglycerol levels were determined by radio-enzymatic assay and lipidomics. Apoptosis was quantified using caspase-3 assays and poly (ADP-ribose) polymerase cleavage. Palmitate oxidation and esterification were determined by [U-14C]palmitate labelling. We found that glucolipotoxicity decreased ELOVL2 content in rodent and human beta cells. Downregulation of ELOVL2 drastically potentiated beta cell apoptosis induced by glucolipotoxicity, whereas adenoviral Elovl2 overexpression and supplementation with DHA partially inhibited glucolipotoxicity-induced cell death in rodent and human beta cells. Inhibition of beta cell apoptosis by the ELOVL2/DHA axis was associated with a decrease in ceramide accumulation. However, the ELOVL2/DHA axis was unable to directly alter ceramide synthesis or metabolism. By contrast, DHA increased palmitate oxidation but did not affect its esterification. Pharmacological inhibition of AMP-activated protein kinase and etomoxir, an inhibitor of carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme in fatty acid β-oxidation, attenuated the protective effect of the ELOVL2/DHA axis during glucolipotoxicity. Downregulation of CPT1 also counteracted the anti-apoptotic action of the ELOVL2/DHA axis. By contrast, a mutated active form of Cpt1 inhibited glucolipotoxicity-induced beta cell apoptosis when ELOVL2 was downregulated. Our results identify ELOVL2 as a critical pro-survival enzyme for preventing beta cell death and dysfunction induced by glucolipotoxicity, notably by favouring palmitate oxidation in mitochondria through a CPT1-dependent mechanism.
Published: 2018
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12. Lipid environment induces ER stress, TXNIP expression and inflammation in immune cells of individuals with type 2 diabetes

Author: Catherine Bernard, Aurélie Carlier, Anne-Françoise Batto, Fabienne Foufelle, Olivier Bourron, Nicolas Venteclef, Anaïs Szpigel, Isabelle Hainault, Pascal Ferré, Eric Hajduch, Alain Ktorza, Jean-François Gautier, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Recherche sur les Cultures Anglophones (LARCA UMR 8225), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiopathologie de la nutrition (LPN), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Pathologies nutritionnelles et métaboliques : obésité et diabète, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Diabétologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de diabétologie [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]
Subjects: 0301 basic medicine, Ceramide, medicine.medical_specialty, Thioredoxin-Interacting Protein, Inflammasomes, THP-1 Cells, Endocrinology, Diabetes and Metabolism, Inflammation, Type 2 diabetes, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Fatty Acids, Monounsaturated, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, NLR Family, Pyrin Domain-Containing 3 Protein, Internal Medicine, medicine, Animals, Humans, Rats, Wistar, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Type 1 diabetes, Dihydroceramide desaturase, Endoplasmic Reticulum Stress, Lipid Metabolism, medicine.disease, Rats, 3. Good health, Oxidative Stress, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, chemistry, 030220 oncology & carcinogenesis, Leukocytes, Mononuclear, Unfolded Protein Response, Unfolded protein response, medicine.symptom, Carrier Proteins, TXNIP
Abstract: Obesity and type 2 diabetes are concomitant with low-grade inflammation affecting insulin sensitivity and insulin secretion. Recently, the thioredoxin interacting protein (TXNIP) has been implicated in the activation process of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we aim to determine whether the expression of TXNIP is altered in the circulating immune cells of individuals with type 2 vs type 1 diabetes and whether this can be related to specific causes and consequences of inflammation. The expression of TXNIP, inflammatory markers, markers of the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress and enzymes involved in sphingolipid metabolism was quantified by quantitative reverse transcription real-time PCR (qRT-PCR) in peripheral blood mononuclear cells (PBMCs) of 13 non-diabetic individuals, 23 individuals with type 1 diabetes and 81 with type 2 diabetes. A lipidomic analysis on the plasma of 13 non-diabetic individuals, 35 individuals with type 1 diabetes and 94 with type 2 diabetes was performed. The effects of ER stress or of specific lipids on TXNIP and inflammatory marker expression were analysed in human monocyte-derived macrophages (HMDMs) and THP-1 cells. The expression of TXNIP and inflammatory and UPR markers was increased in the PBMCs of individuals with type 2 diabetes when compared with non-diabetic individuals or individuals with type 1 diabetes. TXNIP expression was significantly correlated with plasma fasting glucose, plasma triacylglycerol concentrations and specific UPR markers. Induction of ER stress in THP-1 cells or cultured HMDMs led to increased expression of UPR markers, TXNIP, NLRP3 and IL-1β. Conversely, a chemical chaperone reduced the expression of UPR markers and TXNIP in PBMCs of individuals with type 2 diabetes. The lipidomic plasma analysis revealed an increased concentration of saturated dihydroceramide and sphingomyelin in individuals with type 2 diabetes when compared with non-diabetic individuals and individuals with type 1 diabetes. In addition, the expression of specific enzymes of sphingolipid metabolism, dihydroceramide desaturase 1 and sphingomyelin synthase 1, was increased in the PBMCs of individuals with type 2 diabetes. Palmitate or C2 ceramide induced ER stress in macrophages as well as increased expression of TXNIP, NLRP3 and IL-1β. In individuals with type 2 diabetes, circulating immune cells display an inflammatory phenotype that can be linked to ER stress and TXNIP expression. Immune cell ER stress can in turn be linked to the specific exogenous and endogenous lipid environment found in type 2 diabetes.
Published: 2018
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13. Chronic central leptin infusion differently modulates brain and liver insulin signaling

Author: Claude Rouch, Flavien Berthou, Mohammed Taouis, Kyriaki Gerozissis, Arieh Gertler, Centre de Neurosciences Paris-Sud (CNPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Food Science, and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences
Subjects: Blood Glucose, Leptin, Male, Transcription, Genetic, medicine.medical_treatment, Weight Gain, environment and public health, Biochemistry, Eating, 0302 clinical medicine, Endocrinology, Insulin receptor substrate, Insulin, Phosphorylation, Protein Tyrosine Phosphatase, Non-Receptor Type 1, 0303 health sciences, biology, digestive, oral, and skin physiology, Brain, Recombinant Proteins, Liver, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], hormones, hormone substitutes, and hormone antagonists, STAT3 Transcription Factor, medicine.medical_specialty, 030209 endocrinology & metabolism, 03 medical and health sciences, Insulin resistance, Downregulation and upregulation, Internal medicine, medicine, Animals, RNA, Messenger, Molecular Biology, 030304 developmental biology, Leptin receptor, business.industry, medicine.disease, Receptor, Insulin, Rats, enzymes and coenzymes (carbohydrates), Insulin receptor, Insulin Receptor Substrate Proteins, biology.protein, business, Proto-Oncogene Proteins c-akt
Abstract: International audience; Recent studies reported the impact of leptin on peripheral insulin sensitivity and glucose utilization. However, little is known concerning the effect of central leptin on hypothalamic and hepatic insulin efficiency. This study aimed to determine the consequence of chronic intra-cerebroventricular (ICV) leptin or murine leptin antagonist (MLA) infusion on hypothalamic and hepatic insulin signaling pathways, in rats. A 2-week central leptin infusion enhanced insulin-dependent Akt phosphorylation in the liver without changing PTP-1B protein expression, associated to insulin receptor (IR) upregulation and reduced IRS-1 phosphorylation on Ser302 residue. In the hypothalamus, a chronic ICV leptin infusion induced PTP-1B associated with a specific decrease in insulin-dependent Akt phosphorylation. In contrast, a chronic MLA infusion did not alter IR and PTP-1B expressions in hypothalamus and liver. Our results underline a brain leptin-dependent increase in hepatic insulin efficiency as mirrored by IR up-regulation, increased insulin-dependent Akt phosphorylation and reduced IRS-1 phosphorylation on Ser302 residue.
Published: 2011
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14. The Transcription Factor COUP-TFII Is Negatively Regulated by Insulin and Glucose via Foxo1- and ChREBP-Controlled Pathways

Author: Ilham Kharroubi, Anaïs Perilhou, Mireille Vasseur-Cognet, Carole Hénique, Véronique Fauveau, Christophe Magnan, Catherine Postic, Cécile Tourrel-Cuzin, Carina Prip-Buus, Tadahiro Kitamura, Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Earth and Planetary Sciences [Kobe], Kobe University, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Male, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Mice, Obese, FOXO1, COUP Transcription Factor II, Mice, 0302 clinical medicine, Insulin-Secreting Cells, Insulin receptor substrate, Glucokinase, Insulin Secretion, Insulin, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, 0303 health sciences, biology, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Forkhead Box Protein O1, Nuclear Proteins, Forkhead Transcription Factors, Articles, 3. Good health, Insulin oscillation, Liver, 030220 oncology & carcinogenesis, Beta cell, Signal Transduction, medicine.medical_specialty, Down-Regulation, Cell Line, 03 medical and health sciences, Downregulation and upregulation, Internal medicine, medicine, Animals, RNA, Messenger, Molecular Biology, Triglycerides, 030304 developmental biology, Cell Biology, Rats, Mice, Inbred C57BL, Insulin receptor, Glucose, Endocrinology, Hepatocytes, biology.protein, Transcription Factors
Abstract: COUP-TFII has an important role in regulating metabolism in vivo. We showed this previously by deleting COUP-TFII from pancreatic beta cells in heterozygous mutant mice, which led to abnormal insulin secretion. Here, we report that COUP-TFII expression is reduced in the pancreas and liver of mice refed with a carbohydrate-rich diet and in the pancreas and liver of hyperinsulinemic and hyperglycemic mice. In pancreatic beta cells, COUP-TFII gene expression is repressed by secreted insulin in response to glucose through Foxo1 signaling. Ex vivo COUP-TFII reduces insulin production and secretion. Our results suggest that beta cell insulin secretion is under the control of an autocrine positive feedback loop by alleviating COUP-TFII repression. In hepatocytes, both insulin, through Foxo1, and high glucose concentrations repress COUP-TFII expression. We demonstrate that this negative glucose effect involves ChREBP expression. We propose that COUP-TFII acts in a coordinate fashion to control insulin secretion and glucose metabolism.
Published: 2008
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15. Intestinal Gluconeogenesis Is a Key Factor for Early Metabolic Changes after Gastric Bypass but Not after Gastric Lap-Band in Mice

Author: Carine Zitoun, Jocelyne Leclerc, Gilles Mithieux, Bruno Pillot, Benoit Viollet, Fabrizio Andreelli, Véronique Fauveau, Christophe Magnan, A. Duchampt, Xavier Fioramonti, Lara Ribeiro, Roberte Aubert, Stéphanie Troy, Laure Laval, Stéphanie Migrenne, Marc Foretz, Maud Soty, Bernard Thorens, Déterminants génétiques du diabète de type 2 et de ses complications vasculaires ((U 695)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition et cerveau (U1213, U855), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Fédératif de Recherche Alfred Jost (IFRAJ), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nutrition, diabète et cerveau (NUDICE), Université de Lausanne = University of Lausanne (UNIL), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Di Carlo, Marie-Ange
Subjects: Male, medicine.medical_specialty, Time Factors, Gastroplasty, Physiology, medicine.medical_treatment, Gastric Bypass, HUMDISEASE, Biology, Carbohydrate metabolism, medicine.disease_cause, Models, Biological, Eating, Mice, Insulin resistance, Internal medicine, Intestine, Small, medicine, Animals, Insulin, Glucose homeostasis, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Molecular Biology, Glucose Transporter Type 2, Mice, Knockout, Glucose Transporter Type 1, Portal Vein, Gastric bypass surgery, digestive, oral, and skin physiology, Gluconeogenesis, Reproducibility of Results, Type 2 Diabetes Mellitus, Cell Biology, medicine.disease, Dietary Fats, Obesity, Morbid, Mice, Inbred C57BL, Glucose, Endocrinology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Insulin Resistance
Abstract: International audience; Unlike the adjustable gastric banding procedure (AGB), Roux-en-Y gastric bypass surgery (RYGBP) in humans has an intriguing effect: a rapid and substantial control of type 2 diabetes mellitus (T2DM). We performed gastric lap-band (GLB) and entero-gastro anastomosis (EGA) procedures in C57Bl6 mice that were fed a high-fat diet. The EGA procedure specifically reduced food intake and increased insulin sensitivity as measured by endogenous glucose production. Intestinal gluconeogenesis increased after the EGA procedure, but not after gastric banding. All EGA effects were abolished in GLUT-2 knockout mice and in mice with portal vein denervation. We thus provide mechanistic evidence that the beneficial effects of the EGA procedure on food intake and glucose homeostasis involve intestinal gluconeogenesis and its detection via a GLUT-2 and hepatoportal sensor pathway.
Published: 2008
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16. Targeting sphingolipid metabolism in the treatment of obesity/type 2 diabetes

Author: Mélanie Campana, Hervé Le Stunff, Julien Véret, Aurélie Carlier, Christophe Magnan, Rana Mahfouz, Eric Hajduch, Lara Bellini, Université Sorbonne Paris Cité (USPC), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, Ceramide, medicine.medical_treatment, Clinical Biochemistry, Adipose tissue, 030209 endocrinology & metabolism, Apoptosis, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Ceramides, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Internal medicine, Drug Discovery, medicine, Animals, Humans, Sphingosine-1-phosphate, Obesity, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, 0303 health sciences, Sphingolipids, Insulin, Fatty Acids, medicine.disease, Sphingolipid, 3. Good health, Endocrinology, Lipotoxicity, chemistry, Diabetes Mellitus, Type 2, Molecular Medicine, Steatosis, Insulin Resistance, Signal Transduction
Abstract: Obesity is a major factor that is linked to the development of type 2 diabetes (T2D). Excess circulating fatty acids (FAs), which characterize obesity, induce insulin resistance, steatosis, β cells dysfunction and apoptosis. These deleterious effects have been defined as lipotoxicity.FAs are metabolized to different lipid species, including ceramides which play a crucial role in lipotoxicity. The action of ceramides on tissues, such as muscle, liver, adipose tissue and pancreatic β cells, during the development of T2D will also be reviewed. In addition, the potential antagonist action of other sphingolipids, namely sphingoid base phosphates, on lipotoxicity in skeletal muscle and β cells will be addressed.Ceramide is a critical mediator to the development of T2D linked to obesity. Targeting proteins involved in ceramide's deleterious action has not been possible due to their involvement in many other intracellular signaling pathways. A possible means of counteracting ceramide action would be to prevent the accumulation of the specific ceramide species involved in both insulin resistance and β-cell apoptosis/dysfunction. Another possibility would be to adjust the dynamic balance between ceramide and sphingoid base phosphate, both known to display opposing properties on the development of T2D-linked obesity.
Published: 2015
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17. P238 Les acides gras libres jouent un rôle dans la mise en place de la résistance à l'insuline pendant le jeûne et modulent la reprise alimentaire par un effet direct sur le cerveau

Author: Céline Cansell, Luc Pénicaud, Céline Cruciani-Guglielmacci, Nicolas Marsollier, Christophe Magnan, Métabolisme, plasticité et mitochondrie, Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR31-Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de physiopathologie de la nutrition ( LPN ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), ALFEDIAM, Métabolisme Plasticité et Mitochondrie [lié à l'ex IFR 31] (LMPM), IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Endocrinology, Diabetes and Metabolism, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Internal Medicine, 030209 endocrinology & metabolism, General Medicine, 030204 cardiovascular system & hematology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Introduction Le role des nutriments en tant que molecules informatives, ou « nutrient sensing », est fondamental pour le controle de l’homeostasie energetique, et toute modification des concentrations circulantes en nutriment est detectee au niveau du systeme nerveux central (SNC) par des neurones sensibles aux nutriments. Au cours d’un jeune de 24 h, la lipolyse est stimulee et la concentration plasmatique en acides gras libres (AGL) triple, on observe egalement une resistance a l’insuline. Dans cette etude nous avons teste si l’effet des AGL sur le cerveau module la sensibilite a l’insuline et la prise alimentaire suite a la renutrition des animaux apres 24 h de jeune. Materiels et methodes Nous avons constitue un groupe de rats temoins nourris et trois groupes de rats a jeun 24 h : un groupe controle, un groupe perfuse d’acide nicotinique (AN), un inhibiteur de la lipolyse, dans la veine jugulaire, et enfin un groupe ayant 2 perfusions, AN dans la veine jugulaire plus Intralipid/ heparine (IL) dans l’artere carotide en direction du cerveau. Ce dernier groupe permet d’obtenir un modele de rats a jeun ayant une augmentation des AGL au niveau du cerveau uniquement. Les concentrations plasmatiques en AGL et en corps cetoniques ont ete mesurees tout au long de l’etude, et nous avons pratiques des tests de tolerance a l’insuline. Chez d’autres animaux nous avons mesure la prise alimentaire 3 heures apres la renutrition. Resultats La perfusion d’AN, seule ou associe a la perfusion intracarotidienne d’IL, diminue les AGL et les corps cetoniques circulants jusqu’a atteindre les valeurs des temoins nourris. La sensibilite a l’insuline est augmentee dans le groupe AN, qui ne presente pas d’augmentation de l’activite lipolytique, comparee aux temoins a jeun. En revanche le groupe AN + IL presente une sensibilite a l’insuline plus faible, similaire a celle des temoins a jeun. De meme, lors de la renutrition, les rats AN presentent une prise alimentaire plus elevee, tandis que les rats AN + IL ont une prise alimentaire similaire aux temoins a jeun. Conclusion Ces resultats suggerent que les AGL sont des molecules informatives capables de moduler la sensibilite a l’insuline pendant le jeune et la prise alimentaire au moment de la renutrition.

18. Early Neuroendocrine Alterations in Female Rats Following a Diet Moderately Enriched in Fat

Author: Efthimia Kitraki, Kyriaki Gerozissis, George Soulis, Douared, Laetitia, Laboratoire de physiopathologie de la nutrition (LPN), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Blood Glucose, Receptors, Steroid, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, 030209 endocrinology & metabolism, Biology, Weight Gain, Eating, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Stress, Physiological, Corticosterone, Internal medicine, medicine, Animals, Homeostasis, Endocrine system, Hippocampus (mythology), RNA, Messenger, Rats, Wistar, Receptor, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, Reproduction, Insulin, Leptin, Cell Biology, General Medicine, Dietary Fats, Neurosecretory Systems, Rats, Endocrinology, chemistry, Corticosteroid, Female, Energy Metabolism, Luteinizing hormone
Abstract: 1. High-fat diets disrupt metabolic equilibrium and hypothalamic-pituitary-adrenal axis function and may lead to the development of metabolic and endocrine dysfunctions. The early neuroendocrine responses elicited by a combination of short-term metabolic and emotional stressors is not fully elucidated. 2. The purpose of the present study was to determine the impact on female rats, of a short-term enriched in fat diet, combined with an acute stressor. 3. Adult female Wistar rats were fed a fat diet for 7 days and subsequently exposed to 5 min swimming stress. Plasma leptin, insulin, glucose, luteinizing hormone (LH) and corticosterone, along with brain corticosteroid receptors' mRNAs were measured at 1 h post stress. 4. Diet, compared to chow, reduced food intake and body weight gain, increased leptin and LH, and decreased glucose in the periphery. The diet increased plasma corticosterone and reduced GR mRNA in the hippocampus, similarly to swim stress. 5. The diet significantly modified the animals' response to the subsequent swim stress, by blocking further corticosterone rise and GR mRNA reduction. In addition, exposure of diet-fed rats to stress, altered their endocrine response, in terms of leptin and LH. 6. These observations suggest that even short, moderately unbalanced diets can affect peripheral and central components of energy balance, reproduction and stress response.
Published: 2005
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19. Insulinotropic agent ID-1101 (4-hydroxyisoleucine) activates insulin signaling in rat

Author: Christine Rouault, René Gross, Michel Derouet, Céline Cruciani-Guglielmacci, Gérard Reach, M. Manteghetti, Mohammed Taouis, Pierre Petit, Gérard Ribes, Vincent Breil, Christophe Broca, Salwa W. Rizkalla, Bernard Pau, Alain Ktorza, Unité de Recherches Avicoles (URA), Institut National de la Recherche Agronomique (INRA), Neurobiologie de l'Olfaction et de la Prise Alimentaire (NOPA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Génie Biomédical et Diabète Sucré, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de pharmacologie et innovation dans le diabète (CPID), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), Maladies Métaboliques, Institut de Rechercjhes SERVIER, Laboratoire de Neuroendocrinologie Moléculaire de la Prise Alimentaire, Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé (CPBS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration, and Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)
Subjects: insulinémie, MESH: Signal Transduction, Male, Sucrose, Physiology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, MESH: Rats, Zucker, métabolisme nutritionnel, MESH: Rats, Sprague-Dawley, MESH: Isoleucine, rattus rattus, MESH: Glucose Clamp Technique, Rats, Sprague-Dawley, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, MESH: Diabetes Mellitus, Experimental, MESH: Obesity, Insulin, MESH: Animals, ComputingMilieux_MISCELLANEOUS, Euglycemic hyperinsulinemic clamp, chemistry.chemical_classification, MESH: Muscle, Skeletal, 0303 health sciences, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, biology, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Lipids, Amino acid, [SDV] Life Sciences [q-bio], MESH: Glucose, obésité, MESH: Insulin Resistance, nutrition, Liver, Biochemistry, MESH: Hyperinsulinism, Signal transduction, diabète, Signal Transduction, Niacinamide, MESH: Enzyme Activation, medicine.medical_specialty, RAT, 4-HYDROXYISOLEUCINE, MESH: Rats, 030209 endocrinology & metabolism, MESH: Insulin, [INFO] Computer Science [cs], Diabetes Mellitus, Experimental, 03 medical and health sciences, Insulin resistance, MESH: Diet, Hyperinsulinism, Physiology (medical), Internal medicine, medicine, Animals, [INFO]Computer Science [cs], Obesity, Isoleucine, Muscle, Skeletal, résistance à l'insuline, insuline, Pancreatic hormone, 030304 developmental biology, MESH: Sucrose, medicine.disease, MESH: Lipids, MESH: Male, Diet, Rats, Rats, Zucker, Enzyme Activation, Insulin receptor, Glucose, Enzyme, Endocrinology, chemistry, MESH: Phosphatidylinositol 3-Kinases, Glucose Clamp Technique, biology.protein, Insulin Resistance, MESH: Niacinamide, MESH: Liver
Abstract: International audience; ID-1101 (4-hydroxyisoleucine), an amino acid extracted from fenugreek seeds, exhibits an interesting glucose-dependent insulin-stimulating activity. The present study was undertaken to investigate a possible extrapancreatic effect of ID-1101 on insulin signaling and action besides its previously described insulinotropic action. Insulin-sensitizing effects of ID-1101 were investigated in rat in vivo by three different approaches: 1) using euglycemic hyperinsulinemic clamps in two different rat models of insulin resistance, i.e., Zucker fa/fa rats and rats fed a sucrose-lipid diet; 2) measuring liver and muscle phosphatidylinositol (PI) 3-kinase activity after an acute injection of ID-1101 in normal and insulin-resistant diabetic rats; and 3) after chronic treatment in two rat models of insulin resistance. Euglycemic hyperinsulinemic clamp experiments revealed that ID-1101 can improve insulin resistance through an increase of peripheral glucose utilization rate in sucrose-lipid-fed rats and by decreasing hepatic glucose production in Zucker fa/fa rats. Moreover, we demonstrated that a single injection of ID-1101 activates the PI 3-kinase activity in liver and muscle from normal rats but also in muscle from diabetic rats. Finally, chronic ID-1101 treatment significantly reduced insulinemia in type 2 diabetic rats and reduced the progression of hyperinsulinemia in insulin-resistant obese Zucker fa/fa rats. These findings clearly demonstrate that ID-1101 can reduce insulin resistance through activation of the early steps of insulin signaling in peripheral tissues and in liver. In summary, ID-1101, besides its insulinotropic effect, directly improves insulin sensitivity, making it a potentially very valuable therapeutic agent for diabetes treatment.
Published: 2004
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20. Role of Glucose in IRS Signaling in Rat Pancreatic Islets: Specific Effects and Interplay with Insulin

Author: Maryline Paris, Catherine Bernard-Kargar, Nadim Kassis, Alain Ktorza, José Vilar, Berthault, Marie France, Laboratoire de physiopathologie de la nutrition (LPN), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Blood Glucose, Male, medicine.medical_specialty, Insulin Receptor Substrate Proteins, medicine.medical_treatment, 030209 endocrinology & metabolism, In Vitro Techniques, Biology, Islets of Langerhans, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Diazoxide, Animals, Hypoglycemic Agents, Insulin, RNA, Messenger, Phosphorylation, Rats, Wistar, 030304 developmental biology, 0303 health sciences, Messenger RNA, geography, geography.geographical_feature_category, Pancreatic islets, Osmolar Concentration, Intracellular Signaling Peptides and Proteins, General Medicine, Phosphoproteins, Islet, Rats, Endocrinology, medicine.anatomical_structure, Signal transduction, Research Article, Signal Transduction, medicine.drug
Abstract: We investigated the possible interplay between insulin and glucose signaling pathways in rat pancreaticβ-cell with a special focus on the role of glucose in IRS signalingin vivo. Three groups of rats were constituted by combining simultaneous infusion during 48 h either of glucose and/or insulin, or glucose+diazoxide: Hyperglycemic- Hyperinsulinemic (HGHI), euglycemic-Hyperinsulinemic (eGHI), Hyperglycemic-euinsulinemic (HGeI). Control rats were infused with 0,9% NaCl. In HGHI and HGeI rats plasma glucose levels were maintained at 20-22 mmol/l. In eGHI rats, plasma glucose was not different from that of controls, whereas plasma insulin was much higher than in controls. In HGHI rats, IRS-2 mRNA expression, total protein and phosphorylated protein amounts were increased compared to controls. In HGeI rats, only IRS-2 mRNA expression was increased. No change was observed in eGHI rats whatever the parameter considered. In all groups, mRNA concentration of IRS-1 was similar to that of controls. The quantity of total and phosphorylated IRS- 1 protein was dramatically increased in HGHI rats and to a lesser extent in eGHI rats. Neither mRNA nor IRS-1 protein expression were modified in HGeI rats. The data suggest that glucose and insulin play at once a specific and a complementary role in islet IRSs signaling. Especially, glucose stimulates IRS-2 mRNA expression whatever the insulin status and independently of the secretory process. The differential regulation of IRS-1 and IRS-2 expressions is in agreement with their supposed different involvement in the control ofβ-cell growth and function.
Published: 2004
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21. Correction: Proteasome Dysfunction Mediates High Glucose-Induced Apoptosis in Rodent Beta Cells and Human Islets

Author: Stéphane Dalle, Anne Wojtusciszyn, Mathieu Pierre Jean Armanet, Domenico Bosco, Elodie M. Varin, Christophe Broca, Cécile Tourrel-Cuzin, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Eloi, Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Genève (UNIGE), and Hôpital Lapeyronie [Montpellier] (CHU)
Subjects: Male, Gene Expression, lcsh:Medicine, Apoptosis, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biochemistry, 0302 clinical medicine, Cell Signaling, Ubiquitin, Insulin-Secreting Cells, Molecular Cell Biology, Anti-Apoptotic Signaling, lcsh:Science, Apoptotic Signaling Cascade, Cells, Cultured, Protein Metabolism, Cellular Stress Responses, 0303 health sciences, Multidisciplinary, Cell Death, medicine.diagnostic_test, ddc:617, Caspase 3, Mechanisms of Signal Transduction, Endoplasmic Reticulum Stress, Signaling Cascades, 3. Good health, Cell biology, Cell Processes, Carbohydrate Metabolism, Medicine, Metabolic Pathways, Poly(ADP-ribose) Polymerases, Signal transduction, Proteasome Inhibitors, Research Article, Signal Transduction, Proteasome Endopeptidase Complex, Proteolysis, Science, 030209 endocrinology & metabolism, Biology, Glucose Signaling, Stress Signaling Cascade, 03 medical and health sciences, medicine, Animals, Humans, Hypoglycemic Agents, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Venoms, Endoplasmic reticulum, lcsh:R, Biology and Life Sciences, Correction, Cell Biology, Hormones, Rats, Metabolism, Glucose, Proteasome, Hyperglycemia, Unfolded protein response, biology.protein, Exenatide, lcsh:Q, Peptides, Transcription Factor CHOP
Abstract: International audience; The ubiquitin/proteasome system (UPS), a major cellular protein degradation machinery, plays key roles in the regulation of many cell functions. Glucotoxicity mediated by chronic hyperglycaemia is detrimental to the function and survival of pancreatic beta cells. The aim of our study was to determine whether proteasome dysfunction could be involved in beta cell apoptosis in glucotoxic conditions, and to evaluate whether such a dysfunction might be pharmacologically corrected. Therefore, UPS activity was measured in GK rats islets, INS-1E beta cells or human islets after high glucose and/or UPS inhibitor exposure. Immunoblotting was used to quantify polyubiquitinated proteins, endoplasmic reticulum (ER) stress through CHOP expression, and apoptosis through the cleavage of PARP and caspase-3, whereas total cell death was detected through histone-associated DNA fragments measurement. In vitro, we found that chronic exposure of INS-1E cells to high glucose concentrations significantly decreases the three proteasome activities by 20% and leads to caspase-3-dependent apoptosis. We showed that pharmacological blockade of UPS activity by 20% leads to apoptosis in a same way. Indeed, ER stress was involved in both conditions. These results were confirmed in human islets, and proteasome activities were also decreased in hyperglycemic GK rats islets. Moreover, we observed that a high glucose treatment hypersensitized beta cells to the apoptotic effect of proteasome inhibitors. Noteworthily, the decreased proteasome activity can be corrected with Exendin-4, which also protected against glucotoxicity-induced apoptosis. Taken together, our findings reveal an important role of proteasome activity in high glucose-induced beta cell apoptosis, potentially linking ER stress and glucotoxicity. These proteasome dysfunctions can be reversed by a GLP-1 analog. Thus, UPS may be a potent target to treat deleterious metabolic conditions leading to type 2 diabetes.
Published: 2014
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22. In vivo effects of glucose and insulin on secretion and gene expression of glucagon in rats

Author: Nadim Kassis, Luc Pénicaud, Christophe Magnan, Alain Ktorza, M C Laury, Marc Gilbert, J. Philippe, Laboratoire de physiopathologie de la nutrition (LPN), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Métabolisme Plasticité et Mitochondrie [lié à l'ex IFR 31] (LMPM), IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: Blood Glucose, endocrine system, medicine.medical_specialty, medicine.medical_treatment, Glucagon Measurement, 030209 endocrinology & metabolism, Hypoglycemia, Arginine, Glucagon, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Hyperinsulinemia, Animals, Insulin, RNA, Messenger, Rats, Wistar, ComputingMilieux_MISCELLANEOUS, gamma-Aminobutyric Acid, 030304 developmental biology, 0303 health sciences, Chemistry, Glucagon secretion, nutritional and metabolic diseases, medicine.disease, Rats, Glucose, medicine.anatomical_structure, Gene Expression Regulation, Female, Pancreas, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Hyperinsulinism, hormones, hormone substitutes, and hormone antagonists
Abstract: We investigated the effects of insulin and glucose on the control of secretion and gene expression of glucagon in vivo in rats. Animals were studied during 1) a 48-h period of either glucose infusion (hyperglycemia plus hyperinsulinemia; HG-HI rats) or insulin infusion (euglycemia plus hyperinsulinemia; EG-HI rats), and 2) a prolonged postinfusion period in both groups. In HG-HI rats, elevation of plasma insulin and glucose concentrations by about 7 and 5 times, respectively, resulted in a decline in glucagon levels, which fell significantly within 6 h and remained low thereafter, whereas these levels were unchanged in EG-HI rats. Glucagon messenger RNA levels and pancreatic glucagon content were not significantly affected in either HG-HI or EG-HI rats. After cessation of infusions, hypoglycemia occurred in both group of rats. In HG-HI rats, hypoglycemia lasted for about 36 h without any surge in the plasma glucagon level, whereas in EG-HI rats it was transient (approximately 1 h) and stimulated glucagon secretion. In both groups the pancreatic alpha-cell was unresponsive to arginine during the postinfusion period. In conclusion, although a role of intraislet insulin cannot be excluded, glucagon gene expression is insensitive to changes in plasma glucose and insulin concentrations. In contrast, hyperglycemia/hyperinsulinemia, not hyperinsulinemia alone, lowers glucagon secretion and affects the alpha-cell responsiveness to hypoglycemia.
Published: 1995
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23. An integrative and multidisciplinary PNR-PE project for studying Chronic Impact of ED Mixture Exposures at environmental low doses on reproduction, development and behavior

Author: Canivenc Lavier, Marie-Chantal, Applanat , M, Auxiètre, Ta, Babajko, S, Berdal, A, Bergès, Raymond, Boudalia, Sofiane, Chagnon, Marie-Christine, Cravedi, Jean Pierre, Corvol M, Decoq L, ., Desmetz, C., Dhabi, L, Eustache, F, El Sheikh Saad, H, Héliès-Toussaint, Cécile, Lalarme, Elise, Menetrier, Florence, Savouret, Jean-Francois, Pasquis, Bruno, Tiffon, Céline, Auger, Jacques, Waiman, D, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lariboisière-Fernand-Widal [APHP], Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Villa Thuret (UEVT), Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre des Sciences du Goût et de l'Alimentation (CSGA), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and ProdInra, Migration
Subjects: [SDV] Life Sciences [q-bio], [SPI.GPROC] Engineering Sciences [physics]/Chemical and Process Engineering, [SDV]Life Sciences [q-bio], [SDV.IDA]Life Sciences [q-bio]/Food engineering, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, [SDV.IDA] Life Sciences [q-bio]/Food engineering, ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2012

24. Hypothalamic serotonin-insulin signaling cross-talk and alterations in a type 2 diabetic model

Author: Nicolas Vicaire, Eirini M. Markaki, Ioannis K. Papazoglou, D. Bailbé, Claude Rouch, Flavien Berthou, Kyriaki Gerozissis, Bernard Portha, Mohammed Taouis, Centre de Neurosciences Paris-Sud (CNPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire B2PE, Unité BFA, and Université Paris Descartes - Paris 5 (UPD5)
Subjects: Blood Glucose, Leptin, Male, medicine.medical_treatment, Type 2 diabetes, Biochemistry, chemistry.chemical_compound, Eating, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Endocrinology, Insulin, Phosphorylation, Neurotransmitter, 2. Zero hunger, 0303 health sciences, biology, Dexfenfluramine, Postprandial Period, Serotonin Receptor Agonists, Liver, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.drug, medicine.medical_specialty, Serotonin, Hypothalamus, 03 medical and health sciences, Insulin resistance, Internal medicine, Diabetes mellitus, Cell Line, Tumor, medicine, Animals, Humans, Rats, Wistar, Molecular Biology, 030304 developmental biology, Receptor Cross-Talk, medicine.disease, Receptor, Insulin, Rats, Insulin receptor, Disease Models, Animal, chemistry, Diabetes Mellitus, Type 2, biology.protein, Proto-Oncogene Proteins c-akt, 030217 neurology & neurosurgery
Abstract: International audience; Serotonin and insulin are key regulators of homeostatic mechanisms in the hypothalamus. However, in type 2 diabetes, the hypothalamic responsiveness to serotonin is not clearly established. We used a diabetic model, the Goto Kakizaki (GK) rats, to explore insulin receptor expression, insulin and serotonin efficiency in the hypothalamus and liver by means of Akt phosphorylation. Insulin or dexfenfluramine (stimulator of serotonin) treatment induced Akt phosphorylation in Wistar rats but not in GK rats that exhibit down-regulated insulin receptor. Studies in a neuroblastoma cell line showed that serotonin-induced Akt phosphorylation is PI3-kinase dependent. Finally, in response to food intake, hypothalamic serotonin release was reduced in GK rats, indicating impaired responsiveness of this neurotransmitter. In conclusion, hypothalamic serotonin as insulin efficiency is impaired in diabetic GK rats. The insulin-serotonin cross-talk and impairment observed is one potential key modification in the brain during the onset of diabetes.
Published: 2012
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25. Interleukin-7 Regulates Adipose Tissue Mass and Insulin Sensitivity in High-Fat Diet-Fed Mice through Lymphocyte-Dependent and Independent Mechanisms

Author: Laurence Fauconnier, Laurent Héliot, Corentin Spriet, Christophe Magnan, Odile Poulain-Godefroy, Gautier Goormachtigh, Claude Auriault, Renata Polakowska, Solenne Taront, Isabelle Wolowczuk, Stéphanie Lucas, Philippe Froguel, Laurence Macia, Anne Delanoye, Alain Ktorza, Pasquine Saule, Claudie Verwaerde, James P. Di Santo, Jamileh Movassat, Myriam Delacre, Médecine cellulaire et moléculaire (MCM), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Immunopathologie cellulaire des maladies infectieuses (ICMI), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] (IRI), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé-Université de Lille, Sciences et Technologies, Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Immunité Innée, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), The work was supported by the Pasteur Institute in Lille, the Institut Fédératif de Recherche 142 and the Centre National de la Recherche Scientifique. S. L. was supported by a post-doctoral grant from the French Région Nord/Pas-de-Calais., Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER], and Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T]
Subjects: Male, Anatomy and Physiology, B Cells, Mouse, medicine.medical_treatment, Adipose tissue, lcsh:Medicine, White adipose tissue, Mice, SCID, Monocytes, Mice, 0302 clinical medicine, Endocrinology, Lymphocyte homeostasis, Immune Physiology, Glucose homeostasis, Lymphocytes, lcsh:Science, 0303 health sciences, Multidisciplinary, Interleukin, food and beverages, Organ Size, Animal Models, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Cytokines, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, lipids (amino acids, peptides, and proteins), hormones, hormone substitutes, and hormone antagonists, Research Article, medicine.medical_specialty, Adipose Tissue, White, Immune Cells, Immunology, Blood sugar, Endocrine System, Immunopathology, Biology, Diet, High-Fat, Protective Agents, 03 medical and health sciences, Insulin resistance, Model Organisms, Internal medicine, Glucose Intolerance, medicine, Animals, Humans, Obesity, 030304 developmental biology, Nutrition, Inflammation, Diabetic Endocrinology, Receptors, Interleukin-7, Endocrine Physiology, Insulin, Interleukin-7, lcsh:R, Immunity, nutritional and metabolic diseases, Feeding Behavior, Molecular Development, Diabetes Mellitus Type 2, medicine.disease, Mice, Inbred C57BL, Immune System, Metabolic Disorders, lcsh:Q, Clinical Immunology, Insulin Resistance, Stromal Cells, Physiological Processes, Energy Metabolism, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; Although interleukin (IL)-7 is mostly known as a key regulator of lymphocyte homeostasis, we recently demonstrated that it also contributes to body weight regulation through a hypothalamic control. Previous studies have shown that IL-7 is produced by the human obese white adipose tissue (WAT) yet its potential role on WAT development and function in obesity remains unknown. Here, we first show that transgenic mice overexpressing IL-7 have reduced adipose tissue mass associated with glucose and insulin resistance. Moreover, in the high-fat diet (HFD)-induced obesity model, a single administration of IL-7 to C57BL/6 mice is sufficient to prevent HFD-induced WAT mass increase and glucose intolerance. This metabolic protective effect is accompanied by a significant decreased inflammation in WAT. In lymphocyte-deficient HFD-fed SCID mice, IL-7 injection still protects from WAT mass gain. However, IL-7-triggered resistance against WAT inflammation and glucose intolerance is lost in SCID mice. These results suggest that IL-7 regulates adipose tissue mass through a lymphocyte-independent mechanism while its protective role on glucose homeostasis would be relayed by immune cells that participate to WAT inflammation. Our observations establish a key role for IL-7 in the complex mechanisms by which immune mediators modulate metabolic functions.
Published: 2012
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26. Effect of engineered nanoparticles on vasomotor responses in rat intrapulmonary artery

Author: Etienne Roux, Patrick Brochard, Mireille Canal-Raffin, Arnaud Courtois, Thomas Ducret, Francelyne Marano, Christelle Guibert, Yannick Ladeiro, Françoise Rogerieux, Ghislaine Lacroix, Roger Marthan, Pascal Andujar, Bernard Muller, I. Baudrimont, USC 1366 Oenologie, Institut National de la Recherche Agronomique (INRA), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de l'Environnement Industriel et des Risques (INERIS), Physiopathologie de la réactivite bronchique et vasculaire, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de la réactivité bronchique et vasculaire, Laboratoire Santé Travail Environnement, Université Bordeaux Segalen - Bordeaux 2-IFR99, CHU Bordeaux [Bordeaux], Université Paris Diderot - Paris 7 (UPD7), Université de Bordeaux Ségalen [Bordeaux 2], Service de pneumologie et pathologie professionnelle, CHI Créteil, Laboratoire de Cytophysiologie et Toxicologie Cellulaire, Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Guellaen, Georges, Œnologie, Institut National de la Recherche Agronomique (INRA)-Université Victor Segalen - Bordeaux 2, Unité de Recherche Oenologie [Villenave d'Ornon], and Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)
Subjects: Male, Contraction (grammar), Vasodilator Agents, [SDV]Life Sciences [q-bio], 02 engineering and technology, MESH: Rats, Sprague-Dawley, Toxicology, Endoplasmic Reticulum, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Dose-Response Relationship, Drug, Rats, Sprague-Dawley, chemistry.chemical_compound, Vasoconstrictor Agents, MESH: Animals, MESH: Isometric Contraction, ComputingMilieux_MISCELLANEOUS, Titanium, 0303 health sciences, Inhalation Exposure, Vasomotor, Voltage-dependent calcium channel, Biological activity, 021001 nanoscience & nanotechnology, MESH: Titanium, MESH: Calcium Channels, MESH: Inhalation Exposure, 0210 nano-technology, Acetylcholine, medicine.drug, medicine.medical_specialty, Thapsigargin, MESH: Rats, MESH: Pulmonary Artery, chemistry.chemical_element, MESH: Carbon, Calcium, Pulmonary Artery, 03 medical and health sciences, MESH: Vasoconstrictor Agents, In vivo, MESH: Endoplasmic Reticulum, Internal medicine, Isometric Contraction, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Rats, Wistar, 030304 developmental biology, Pharmacology, Dose-Response Relationship, Drug, MESH: Rats, Wistar, Carbon, MESH: Male, Rats, MESH: Vasodilator Agents, Endocrinology, chemistry, Nanoparticles, Calcium Channels, MESH: Nanoparticles, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Pulmonary circulation could be one of the primary vascular targets of finest particles that can deeply penetrate into the lungs after inhalation. We investigated the effects of engineered nanoparticles on vasomotor responses of small intrapulmonary arteries using isometric tension measurements. Acute in vitro exposure to carbon nanoparticles (CNP) decreased, and in some case abolished, the vasomotor responses induced by several vasoactive agents, whereas acute exposure to titanium dioxide nanoparticles (TiO(2)NP) did not. This could be attributed to a decrease in the activity of those vasoactive agents (including PGF(2)(alpha), serotonin, endothelin-1 and acetylcholine), as suggested when they were exposed to CNP before being applied to arteries. Also, CNP decreased the contraction induced by 30 mM KCl, without decreasing its activity. After endoplasmic reticulum calcium stores depletion (by caffeine and thapsigargin), CaCl(2) addition induced a contraction, dependent on Store-Operated Calcium Channels that was not modified by acute CNP exposure. Further addition of 30 mM KCl elicited a contraction, originating from activation of Voltage-Operated Calcium Channels that was diminished by CNP. Contractile responses to PGF(2)(alpha) or KCl, and relaxation to acetylcholine were modified neither in pulmonary arteries exposed in vitro for prolonged time to CNP or TiO(2)NP, nor in those removed from rats intratracheally instilled with CNP or TiO(2)NP. In conclusion, prolonged in vitro or in vivo exposure to CNP or TiO(2)NP does not affect vasomotor responses of pulmonary arteries. However, acute exposure to CNP decreases contraction mediated by activation of Voltage-Operated, but not Store-Operated, Calcium Channels. Moreover, interaction of some vasoactive agents with CNP decreases their biological activity that might lead to misinterpretation of experimental data.
Published: 2010
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27. Localized SOI Logic and Bulk I/O devices co-integration for Low Power System-on-Chip Technology

Author: C. Borowiak, Stephane Denorme, M.-P. Samson, L. Clement, Francois Leverd, G. Bidal, Sébastien Barnola, F. Abbate, K. Benotmane, Y. Campidelli, C. Fenouillet-Beranger, Thomas Skotnicki, Frederic Boeuf, Gerard Ghibaudo, Stephane Monfray, Dominique Golanski, P. Perreau, J.-L. Huguenin, Nicolas Loubet, STMicroelectronics [Crolles] (ST-CROLLES), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Microélectronique, Electromagnétisme et Photonique - Laboratoire d'Hyperfréquences et Caractérisation (IMEP-LAHC), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Domenget, Chahla, and Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Materials science, Silicon, [SPI.NANO] Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, chemistry.chemical_element, Silicon on insulator, Hardware_PERFORMANCEANDRELIABILITY, 02 engineering and technology, 01 natural sciences, law.invention, Stack (abstract data type), law, Low-power electronics, 0103 physical sciences, Hardware_INTEGRATEDCIRCUITS, Wafer, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, ComputingMilieux_MISCELLANEOUS, 010302 applied physics, business.industry, Transistor, Electrical engineering, 021001 nanoscience & nanotechnology, chemistry, Logic gate, Optoelectronics, 0210 nano-technology, Tin, business
Abstract: The objective of this paper is to present the successful co-integration of Logic Ultra-Thin Body and Box (UTBB) devices and bulk-Si I/O devices on the same chip. The UTBB transistors are integrated locally on a Bulk wafer with the Localized Silicon On Insulator (LSOI) process technology with HfO 2 /TiN gate stack for low power applications. I/O co-integrated Bulk devices have a thicker interfacial SiO 2 under the HfO 2 /TiN stack to be compatible with the I/O higher voltage. Both performances of logic UTBB and I/O bulk devices are presented.
Published: 2010

28. Hybrid Localized SOI/Bulk technology for Low Power System-on-Chip

Author: G. Bidal, Ph. Galy, O. Faynot, L. Clement, Frederic Boeuf, A. Bajolet, Antoine Cros, S. Handler, D. Marin-Cudraz, Christian Arvet, Qing Liu, Francois Leverd, Y. Campidelli, Stephane Denorme, Gerard Ghibaudo, F. Abbate, Sébastien Barnola, Stephane Monfray, J.-L. Huguenin, M.-P. Samson, Claire Fenouillet-Beranger, Nicolas Loubet, T. Benoist, K. Benotmane, Thomas Skotnicki, C. Borowiak, P. Perreau, STMicroelectronics [Crolles] (ST-CROLLES), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Interactions et dynamique des environnements de surface (IDES), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Science et Ingénierie des Matériaux et Procédés (SIMaP), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Microélectronique, Electromagnétisme et Photonique - Laboratoire d'Hyperfréquences et Caractérisation (IMEP-LAHC), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), and Domenget, Chahla
Subjects: 010302 applied physics, Materials science, Electrostatic discharge, business.industry, Electrical engineering, Silicon on insulator, Hardware_PERFORMANCEANDRELIABILITY, Chip, 01 natural sciences, Silicon-germanium, chemistry.chemical_compound, chemistry, [PHYS.COND.CM-GEN] Physics [physics]/Condensed Matter [cond-mat]/Other [cond-mat.other], Logic gate, Low-power electronics, [PHYS.COND.CM-GEN]Physics [physics]/Condensed Matter [cond-mat]/Other [cond-mat.other], 0103 physical sciences, Optoelectronics, System on a chip, Static random-access memory, business, ComputingMilieux_MISCELLANEOUS
Abstract: This paper highlights the successful co-integration of Localized Silicon-On-Insulator (LSOI) devices and of bulk-Si I/O devices on the same chip. LSOI devices present good logic performances and very low mismatch values down to 1.2mV/µm. In addition, we show the backbiasing impact on LSOI SRAM bit-cells for stability improvement. This work also presents the co-integration of LSOI with bulk devices as a solution for the devices that are not compatible with thin-body technology. In particular, we demonstrate for the first time competitive bulk co-integrated ElectroStatic Discharge (ESD) protections.
Published: 2010

29. Gate-All-Around technology: taking advantage of ballistic transport?

Author: Bidal, G., Huguenin, J.L., Denorme, S., Fleury, D., Loubet, N., Pouydebasque, A., Perreau, P., Leverd, F., Barnola, S., Beneyton, R., Orlando, B., Gouraud, P., Salvetat, T., Clement, L., Monfray, S., Boeuf, F., Skotnicki, T., Département Mécanismes d'Accidents (INRETS/MA), Institut National de Recherche sur les Transports et leur Sécurité (INRETS), Institut d'Astrophysique de Paris (IAP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Domenget, Chahla
Subjects: [SPI.NANO] Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2009

30. High velocity Si-nanodot : a candidate for SRAM applications at 16nm node and below

Author: Bidal, G., Boeuf, F., Denorme, S., Loubet, N., Leverd, F., Lagrasta, S., Orlando, B., Beneyton, R., Clement, L., Pantel, R., Monfray, S., Skotnicki, T., Institut d'Astrophysique de Paris (IAP), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), STMicroelectronics [Crolles] (ST-CROLLES), Domenget, Chahla, and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SPI.NANO] Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2009

31. The prediabetic period is characterized by islet microangiopathy in the Goto-Kakizaki rat, a spontaneous model of type 2 diabetes

Author: Homo-Delarche, Françoise, Giroix, M.H., Lacraz, G., Calderari, Sophie, Cornut, M., Ehses, J.A., Schmidlin, F., Coulaud, J., Gangnerau, M.N., Serradas, P., Irminger, J.C., Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Angiogénèse embryonnaire et pathologique, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Labex MemoLife, Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Genève (UNIGE), Division of Endocrinology and Diabetes, University of Oklahoma Health Sciences Center (OUHSC), Merck Serono, Merck & Co. Inc, Metabolisme et Differenciation Intestinale, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), European Association for the Study of Diabetes (EASD). GBR., Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre interdisciplinaire de recherche en biologie (CIRB), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Labex MemoLife, Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Genève = University of Geneva (UNIGE)
Subjects: [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Endothelial signals are essential during pancreas development. Goto-Kakizaki (GK) rats have a 70% decrease in β-cell mass at E18, while it is similar at E13 to that of Wistar control rats. Because adult diabetic GK rats are hypercholesterolemic, we hypothesized that maternal hypercholesterolemia together with maternal/fetal hyperglycemia might alter perinatal pancreas development through islet microangiopathy (atherosclerosis) programming. Our aims were to: 1) demonstrate alterations of vascularisation in islets from 1-week-old GK rats, during the so-called prediabetic period; 2) measure systemic levels of lipids and various cytokines and chemokines around birth. Sera were obtained from 1-week-old male Wistar and GK rats (except otherwise stated) for radioimmunoassays; 2) Islets from these rats were hand-picked after collagenase digestion; 3) Molecular approaches included Affymetrix gene array and low density arrays targeted at endothelium, angiogenesis and cardiovascular disease biomarkers (OligoGEArrayRat). Gene expression was confirmed by qRT-PCR. Results: Affymetrix gene array (230A) showed differential expression of several genes which might be involved in inflammation in GK versus Wistar islets. Notably, the gene encoding epoxide hydrolase, the enzyme responsible for epoxyeicosatrienoic acids (EETs) conversion was decreased by 90%. EETs have anti-inflammatory and protective vascular effects. We then analysed expression of genes present on the 3 targeted arrays mentioned above (128 different genes/array). We obtained 20 up- and 8 down-regulated genes. Among the up-regulated genes were those encoding: caspase 1 (IL-1-converting enzyme, x10) that cleaves IL-1 and IL-18 into their active forms; various cytokines/chemokines involved in macrophage/granulocyte movements: CXCL2 (MIP-2α, x4.1), CXCL-1 (chemokine KC, x3.9), IL-15 (x1.4) and IL- 18 (x3.7); also fibronectin 1 (x2.3), ICAM-1 (x2.6), VEGFR3 (x2), carboxypeptidase 2 (TAFI, x1.9) and angiotensinogen (x1.9). These 3 groups have pro-atherosclerotic effects. Among the down-regulated genes were those encoding: osteoproteogerin (x0.4), neuropilin 1 (x0.6), platelet-derived growth factor (x0.6), coagulation factor III (tissue factor, x0.4) and the neuropeptide Y (x0.1) that acts as vascular mitogen. These data suggest that angiogenesis is deficient in neonatal GK islets. Concomitantly, prediabetic 1-week old-GK rats had lower leptin and higher circulating cholesterol/HDL ratio, MCP-1 and MIP-1α levels than Wistar rats. The latter data might reflect systemic vascular disturbances in GK neonates. Soon after birth many pro-atherosclerotic genes were upregulated in GK islets, while pro-angiogenic genes were downregulated. These data highlight early deficient islet vascularisation that might be responsible for the GK β-cell mass defect and therefore may be of potential therapeutic value.
Published: 2008

32. Intrauterine programming of beta cell development and function by maternal diabetes. What does embryo-transfer experiments in GK/Par rats tell us?

Author: Chavey, A., Gangnereau, M.-N., Maulny, Linda, Bailbé, D., Movassat, J., Renard, Jean Paul, Portha, B., Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Biologie du développement et reproduction (BDR), and Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)
Subjects: [SDV]Life Sciences [q-bio], RAT, DIABETES, [INFO]Computer Science [cs], ComputingMilieux_MISCELLANEOUS, INSULIN SECRETION, BETA-CELL
Abstract: International audience
Published: 2008

33. 4,4-Dimethyl-1,2,3,4-tetrahydroquinline-based PPARΑ/Γ agonists. Part I: Synthesis and pharmacological evaluation

Author: Catherine Dacquet, Nathalie Hennuyer, Valérie Audinot-Bouchez, Marie-Claude Viaud-Massuard, Bart Staels, Jean-Albert Boutin, Daniel-Henri Caignard, Cécile Parmenon, Jérôme Guillard, Alain Ktorza, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Agonist, medicine.drug_class, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Pharmaceutical Science, 010402 general chemistry, 01 natural sciences, Biochemistry, Chemical synthesis, PPAR agonist, Structure-Activity Relationship, Insulin resistance, Drug Discovery, medicine, Hypoglycemic Agents, PPAR alpha, Receptor, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Molecular Structure, 010405 organic chemistry, Chemistry, Organic Chemistry, Peroxisome, medicine.disease, In vitro, 0104 chemical sciences, 3. Good health, PPAR gamma, Nuclear receptor, Quinolines, Molecular Medicine
Abstract: Type-2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance in the liver and peripheral tissues accompanied by a defect in pancreatic beta-cell. Since their discovery three subtypes of Peroxisomes Proliferators Activated Receptors were identified namely PPARalpha, PPARgamma and PPARbeta/(delta). We were interested in designing novel PPARgamma selective agonists and/or dual PPARalpha/gamma agonists. Based on the typical topology of synthetic PPAR agonists, we focused our design approach on 4,4-dimethyl-1,2,3,4-tetrahydroquinoline as novel cyclic tail.
Published: 2008

34. Follow-up of GK rats during prediabetes highlights increased insulin action and fat deposition despite low insulin secretion

Author: Eric Bertin, Jamileh Movassat, Danièle Bailbé, Françoise Picarel-Blanchot, Jacques Mourot, Bernard Portha, Cécile Lubrano-Berthelier, Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Systèmes d'élevage, nutrition animale et humaine (SENAH), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Blood Glucose, tolérance au glucose, Physiology, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, tissu adipeux, rattus rattus, 0302 clinical medicine, Insulin Secretion, Body Fat Distribution, Insulin, Prediabetes, 2. Zero hunger, RAT, RAT GOTO-KAKIZAKI, 0303 health sciences, Glucose tolerance test, medicine.diagnostic_test, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, Animals, Suckling, sensibilité à l'insuline, Adipose Tissue, Endocrinologie et métabolisme, Body Composition, Female, diabète, medicine.medical_specialty, 030209 endocrinology & metabolism, Biology, Rats, Mutant Strains, 03 medical and health sciences, Insulin resistance, In vivo, Physiology (medical), Diabetes mellitus, Internal medicine, Hyperinsulinism, Glucose Intolerance, medicine, Animals, Secretion, nutrition animale, Rats, Wistar, Pancreatic hormone, insuline, 030304 developmental biology, Endocrinology and metabolism, composition corporelle, Glucose Tolerance Test, medicine.disease, Rats, Disease Models, Animal, Endocrinology, Animals, Newborn, Diabetes Mellitus, Type 2, Insulin Resistance
Abstract: International audience; The adult Goto-Kakizaki (GK) rat is characterized by impaired glucose-induced insulin secretion in vivo and in vitro, decreased beta-cell mass, decreased insulin sensitivity in the liver, and moderate insulin resistance in muscles and adipose tissue. GK rats do not exhibit basal hyperglycemia during the first 3 wk after birth and therefore could be considered prediabetic during this period. Our aim was to identify the initial pathophysiological changes occurring during the prediabetes period in this model of type 2 diabetes (T2DM). To address this, we investigated beta-cell function, insulin sensitivity, and body composition in normoglycemic prediabetic GK rats. Our results revealed that the in vivo secretory response of GK beta-cells to glucose is markedly reduced and the whole body insulin sensitivity is increased in the prediabetic GK rats in vivo. Moreover, the body composition of suckling GK rats is altered compared with age-matched Wistar rats, with an increase of the number of adipocytes before weaning despite a decreased body weight and lean mass in the GK rats. None of these changes appeared to be due to the postnatal nutritional environment of GK pups as demonstrated by cross-fostering GK pups with nondiabetic Wistar dams. In conclusion, in the GK model of T2DM, beta-cell dysfunction associated with increased insulin sensitivity and the alteration of body composition are proximal events that might contribute to the establishment of overt diabetes in adult GK rats.
Published: 2007
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35. Type 2 diabetes - a matter of failing beta-cell neogenesis? Clues from the GK rat model

Author: Jamileh Movassat, Sophie Calderari, C. Plachot, E. Fernández, Carmen Álvarez, Bernard Portha, M. N. Gangnerau, Miguel Ángel Chaves Martín, F. Escrivá, Patricia Serradas, Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM)
Subjects: Blood Glucose, medicine.medical_specialty, β-cell mass, Endocrinology, Diabetes and Metabolism, Cellular differentiation, medicine.medical_treatment, 030209 endocrinology & metabolism, Stimulation, Neogenesis, Diabetes Mellitus, Experimental, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Pancreatectomy, Internal medicine, Precursor cell, Insulin-Secreting Cells, Internal Medicine, Medicine, Endocrine system, Animals, Humans, Insulin, Rats, Wistar, Pancreas, 030304 developmental biology, type 2 diabete, 0303 health sciences, biology, business.industry, Regeneration (biology), Type 2 Diabetes Mellitus, Cell Differentiation, Rats, Inbred Strains, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, biology.organism_classification, Rats, Disease Models, Animal, Diabetes Mellitus, Type 2, igfs, gk rat, neogenesis, business, pancreas development, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Now that reduction in beta-cell mass has been clearly established in humans with type 2 diabetes mellitus (T2D), the debate focuses on the possible mechanisms responsible for decreased beta-cell number. Appropriate inbred rodent models are essential tools for this purpose. The information available from the Goto-Kakizaki (GK) rat, one of the best characterized animal models of spontaneous T2D, is reviewed in such a perspective. We propose that the defective beta-cell mass in the GK model reflects mostly a persistently decreased beta-cell neogenesis. The data discussed in this review are consistent with the notion that poor proliferation and/or survival of the endocrine precursor cells during GK foetal life will result in a decreased pool of endocrine precursors in the pancreas, and hence an impaired capacity of beta-cell neogenesis (either primary in the foetus or compensatory in the newborn and the adult). As we also demonstrated that beta-cell neogenesis can be pharmacologically reactivated in the GK model, our work supports, on a more prospective basis, the concept that facilitation of T2D treatment may be obtained through beta-cell mass expansion after stimulation of beta-cell regeneration/neogenesis in diabetic patients.
Published: 2007
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36. A two-week central leptin infusion is not sufficient to induce hypothalamic leptin- or insulin-resistance but is able to induce hypothalamic PTP-1B expression

Author: Berthou, Flavien, Rouch, C., Gertler, Arieh, Djiane, Jean, Gerozissis, Kyriaki, Taouis, Mohammed, Neurobiologie de l'Olfaction et de la Prise Alimentaire (NOPA), Institut National de la Recherche Agronomique (INRA), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Hebrew University of Jerusalem, Université Paris-Sud - Paris 11 (UP11), and ProdInra, Migration
Subjects: [SDV] Life Sciences [q-bio], INSULIN-RESISTANCE, HYPOTHALAMIC PTP-1B EXPRESSION, HYPOTHALAMIC LEPTIN, [SDV]Life Sciences [q-bio], RAT, [INFO]Computer Science [cs], [INFO] Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2007

37. Defective IGF2 and IGF1R protein production in embryonic pancreas precedes beta cell mass anomaly in the Goto-Kakizaki rat model of type 2 diabetes

Author: M. Thibault, M.-J. Meile, Nadim Kassis, S. Calderari, Carmen Álvarez, Patricia Serradas, M.N. Gangnerau, Bernard Portha, Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Biochemistry, and Universität Leipzig [Leipzig]
Subjects: Blood Glucose, Endocrinology, Diabetes and Metabolism, Cellular differentiation, medicine.medical_treatment, Receptor, IGF Type 1, Mice, 0302 clinical medicine, Insulin-Secreting Cells, pancreas, Receptor, 2. Zero hunger, 0303 health sciences, Gene Expression Regulation, Developmental, Cell Differentiation, differentiation, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.anatomical_structure, embryonic structures, Female, Beta cell, Pancreas, gk rat, endocrine system, medicine.medical_specialty, insulin, animal structures, growth, organogenesis, 030209 endocrinology & metabolism, Biology, 03 medical and health sciences, Insulin-Like Growth Factor II, Internal medicine, Internal Medicine, medicine, Animals, Humans, Rats, Wistar, Pancreatic hormone, 030304 developmental biology, Insulin-like growth factor 1 receptor, type 2 diabete, bata cell mass, Insulin, pancreatic rudiment, Embryonic stem cell, Rats, Endocrinology, Diabetes Mellitus, Type 2, NIH 3T3 Cells, igf, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The Goto-Kakizaki (GK) rat is a spontaneous model of type 2 diabetes. Defective beta cell mass detectable in late fetal age precedes the onset of hyperglycaemia. Our hypothesis was that an embryonic IGF production deficiency might be involved in beta cell mass anomaly in the diabetic GK rat. To test this, we evaluated during pancreatic organogenesis: (1) the beta cell development in GK rats on embryonic day (E) 13.5 and E18.5; (2) IGF2 and IGF1 receptor (IGF1R) pancreatic protein production on E13.5 and E18.5; (3) the in vitro development of GK pancreatic rudiment on E13.5; and (4) the in vitro effect of IGF2 addition on beta cell mass. Beta cell quantitative analyses were determined by immunohistochemistry and morphometry. IGF2 and IGF1R pancreatic protein production was evaluated using western blot analyses. Dorsal pancreatic rudiments were dissected on E13.5, separated from surrounding mesenchyme and cultured for 7 days without or with recombinant IGF2. While beta cell mass was already decreased on E18.5, the differentiation of the first beta cells was in fact normal in E13.5 GK pancreas. Moreover, defective IGF2 and IGF1R protein production was detected in GK pancreatic rudiment as early as E13.5. The isolated GK pancreatic rudiment as maintained in vitro mimics the GK beta cell deficiency observed in vivo. This last approach enabled us to show that GK beta cells were fully responsive to IGF2 as far as their net growth is concerned. In diabetic GK rat, defective IGF2 and IGF1R protein production in embryonic pancreas precedes beta cell mass anomaly. IGF2 supplementation expands the pool of beta cells.
Published: 2007
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38. The spontaneously decreased beta cell mass and pancreatic IGF2 production in the GK fetal rat are both improved in response to maternal undernutrition

Author: Fernandez, E., Gangnereau, M.N., Calderari, Sophie, De Miguel, L., Serradas, P., ESCRIVA, F., Portha, B., Alvarez, C., ProdInra, Migration, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and European Association for the Study of Diabetes (EASD). GBR.
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, reproductive and urinary physiology
Abstract: International audience; The Goto-Kakizaki (GK) rat is a spontaneous model of type 2 diabetes with a defective beta-cell mass detectable in late fetal development (21.5 days postcoitum [dpc]) and the diminished IGF- 2 production seems to be involved in this effect. Since we have previously shown that early undernutrition increases beta-cell mass in foetuses at term, the aim of the present study was to investigate whether a condition of maternal malnutrition might similarly positively modulate the beta-cell mass in GK foetuses. In addition, the implication of the IGF system, which is highly responsive to nutritional status in these processes was evaluated. To this end, we have measured in 21.5 dpc undernourished GK foetuses (GK-U) 1) serum GH and IGF levels, 2) beta-cell mass, 3) replication and differentiation of beta-cells, and 4) IGF-1 and -2 protein content in liver and pancreas. All values were compared to those in control GK foetuses. GK rats were obtained from our colony of GK/Par rats. Pregnant GK females were food restricted (65% restriction) during the last week of gestation. Serum concentrations of GH, IGF-1 and -2 were measured by radioimmunoassay. Beta-cell mass, beta-cell differentiation and beta-cell replication were evaluated using quantitative immunohistochemistry methods. The protein content of IGF-1 and -2 was analyzed by western blot in pancreas and liver. Although in no case the GK-U values reached the levels of control Wistar rats, the results show that beta-cell mass increased by 90% in GK-U foetuses as compared to the GK group and that both beta-cell neogenesis and replication were stimulated as well. On the other hand, similar serum GH, IGF-1 and -2 levels were observed in GK and GK-U foetuses. Malnutrition affected IGF protein content in the various tissues studied. Particularly relevant was a 3-fold increase of pancreatic IGF-2 protein levels in GK-U foetuses. Our data suggest that 1) maternal malnutrition increased betacell mass and pancreatic IGF-2 protein levels in GK-U foetuses at 21.5 dpc, 2) the increased beta-cell mass could be related to the stimulation of both betacell neogenesis and beta-cell replication, 3) the locally increased pancreatic IGF-2 may be instrumental in these processes. They also illustrate for the first time that enhanced IGF-2 production in the pancreas can be triggered by a nutritional manipulation of the mother. So far it is not known whether or not undernutrition of the mother is sufficient to delay/decrease the risk of the GK/Par rat for developing overt hyperglycaemia at adult age.
Published: 2007

39. Transgenic expression of human INS gene in Ins1/Ins2 double knockout mice leads to insulin underproduction and diabetes in some male mice

Author: Danielle Bucchini, Gretta Abou Sleymane, Laëtitia Languille, Loïc Leroux, Alain Ktorza, Susan Saint-Just, Cécile Tourrel-Cuzin, Rajiv L. Joshi, Luciane Lamotte, Melis Karaca, Béatrice Durel, Laboratoire de physiopathologie de la nutrition (LPN), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and Douared, Laetitia
Subjects: Genetically modified mouse, Blood Glucose, Male, medicine.medical_specialty, Transgene, medicine.medical_treatment, Gene Expression, 030209 endocrinology & metabolism, Biology, Animals, Genetically Modified, 03 medical and health sciences, Diabetes mellitus genetics, Mice, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Conditional gene knockout, Gene expression, Glucose Intolerance, medicine, Diabetes Mellitus, Animals, Humans, Insulin, Pancreas, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, medicine.disease, medicine.anatomical_structure, Endocrinology, Female
Abstract: We have generated transgenic mouse lines expressing exclusively a human INS transgene on an Ins1/Ins2 double knockout (mIKO) background. The transgene expression was driven by either a 4000 bp or a 353 bp promoter. These transgenic lines, designated mIKO:INS4000 and mIKO:INS353, were viable and fertile. Determination of the amounts of insulin transcripts and total pancreatic insulin content revealed relative insulin underproduction in both lines, from birth to adulthood. Total pancreatic insulin stores in mIKO:INS4000 and mIKO:INS353 mice represented only about 50% and 27%, respectively, as compared to wild-type mice. Morphometric analysis of pancreas did not show any compensatory beta-cell hyperplasia. The majority of animals in both lines remained normoglycemic throughout their lives. Nevertheless, glucose tolerance tests revealed glucose intolerance in nearly half of mIKO:INS4000 male mice, likely due to impaired insulin secretion detected in those animals. In addition, a small fraction (2-4%) of male mice in both lines spontaneously developed diabetes with very distinct pathophysiological features. Diabetes was never seen in female animals. The diabetes developed by mIKO:INS353 mice was rapidly lethal, accompanied by a dramatic depletion of pancreatic insulin stores whereas the mIKO:INS4000 diabetic animals could live for several months. This suggests a possible link between the structure of the human INS gene promoter and the type of diabetes developed in these lines.
Published: 2006

40. Brain insulin signaling regulation by leptin and serotonin. Potential impact on the development of metabolic diseases

Author: Gerozissis, Kyriaki, Banas, S.M., Berthou, Flavien, Bailleux, Virginie, Rouch, C., Taouis, Mohammed, Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie de l'Olfaction et de la Prise Alimentaire (NOPA), Institut National de la Recherche Agronomique (INRA), and Université Paris-Sud - Paris 11 (UP11)
Subjects: [SDV]Life Sciences [q-bio], SYSTEME NERVEUX CENTRAL, SEROTONIN, RAT, NUTRITION, [INFO]Computer Science [cs], ComputingMilieux_MISCELLANEOUS, BRAIN INSULIN
Abstract: International audience
Published: 2006

41. Defective IGF-2 and IGF-1R protein expressions in pancreatic rudiment precede beta cell mass anomaly in GK rat

Author: Calderari, Sophie, Gangnereau, M.N., Thibault, M., Meile, M.J., Alvarez, C., Portha, B., Serradas, P., Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), European Association for the Study of Diabetes (EASD). GBR., and ProdInra, Migration
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, embryonic structures, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The Goto-Kakizaki (GK) rat is a spontaneous model of type 2 diabetes with a defective betacell mass detectable in late fetal age. To determine the involvement of IGF-2 in this defect, we evaluated during GK pancreatic organogenesis: 1) the GK beta-cell development on embryonic day (E) 13.5 and E18.5; 2) IGF-2 and IGF-1 receptor (IGF-1R) pancreatic protein expressions at E13.5 and E18.5; 3) the in vitro development of E13.5 GK pancreatic rudiment; 4) the effect of IGF-2 addition on beta-cell mass in pancreatic rudiment in vitro. GK rats were obtained from our local colony. Wistar (W) rats were used as control. Beta-cell quantitative analyses were determined by immunohistochemistry and morphometry at E13.5, E18.5 and in pancreatic rudiments after culture. IGF-2 and IGF-1R pancreatic protein expressions were evaluated using Western blot analyses at E13.5 and E18.5. For culture experiments, dorsal pancreatic rudiments were dissected at E13.5, separated from its surrounding mesenchyme and cultured for 7 days onto three-dimensional collagen gel at 5.5 mM of glucose. Recombinant IGF-2 (100 ng/ml) was added every day to the culture medium. To label cells in the S phase, BrdU was added to the culture medium one hour before the end of the culture. Apoptosis in pancreatic rudiment was evaluated using the ApopTag kit. The number of beta-cell was normal in GK pancreatic rudiment at E13.5. However, pancreatic beta-cell mass was decreased by 74% in E18.5 GK as compared to W control at the same age. 2) IGF-2 and IGF-1R protein expressions were respectively decreased by 27% and 42% in E13.5 GK pancreatic rudiments as compared to W controls. Again, IGF-2 and IGF-1R pancreatic protein expressions were decreased (by 58% and 34% respectively) in GK at E18.5 as compared to W values. 3) After 7 days of culture, GK pancreatic rudiments exhibited a beta-cell number reduced by 78%. This beta-cell defect was similar to that observed in E18.5 GK. After culture, the total pancreatic-cell and the beta-cell proliferation rates in GK pancreatic rudiment were decreased respectively by 27% and by 40% as compared to W values. Moreover, the apoptotic rate of total cells was increased by 42% in GK pancreatic rudiment after culture. 4) The daily addition of IGF-2 to GK pancreatic rudiment increased the beta-cell number by 123%, the total cell proliferation rate by 55%, and the beta-cell proliferation rate by 111% as compared to GK pancreatic rudiment cultured without IGF-2. Taken together these data show that while beta-cell mass is already decreased at E18.5, the differentiation of the first beta cells is in fact normal in E13.5 GK pancreas. Thus, a defective IGF-2 and IGF-1R protein expressions within the GK pancreatic rudiment represent a primary anomaly. The isolated GK pancreatic rudiment as maintained in vitro under the conditions here described, mimicks the GK beta-cell deficiency as observed in vivo. This in vitro approach was useful to highlight the effect of an IGF-2 supplementation on GK beta-cell growth. Moreover, it also suggests that, IGF signaling pathway seems to be functional in GK beta cells in response to IGF-2.
Published: 2006

42. Pancreatic islets of diabetic GK rat exhibit an unexpected resistance to oxidative stress

Author: Lacraz, Grégory, Bailbe, Danièle, Calderari, Sophie, Irminger, Jean-Claude, Serradas, Patricia, Portha, Bernard, Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Genetic Medicine and Development, Université de Genève (UNIGE), American Diabetes Association (ADA). USA., and ProdInra, Migration
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2006

43. La néoglucogenèse intestinale: nouvel acteur du controle de la prise alimentaire

Author: Mithieux, G., Magnan, Christophe, Laboratoire de physiopathologie de la nutrition (LPN), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and Berthault, Marie France
Published: 2006

44. Islet inflammation and fibrosis in a spontaneous model of type 2 diabetes, the GK rat

Author: Philippe A. Halban, Josiane Coulaud, Françoise Homo-Delarche, Sophie Calderari, Patricia Serradas, Bernard Portha, Marie-Noëlle Gangnerau, Jean-Claude Irminger, Manuel Dolz, Katharina Rickenbach, Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Genève (UNIGE), and Université Paris Diderot - Paris 7 (UPD7)
Subjects: Male, Inflammation/genetics/immunology/metabolism, endocrine system diseases, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Extracellular matrix, Diabetes Mellitus, Type 2/genetics/metabolism/ pathology, 0302 clinical medicine, Fibrosis, Oligonucleotide Array Sequence Analysis, ddc:616, 0303 health sciences, geography.geographical_feature_category, CD68, Reverse Transcriptase Polymerase Chain Reaction, Islet, Immunohistochemistry, Extracellular Matrix, 3. Good health, medicine.symptom, medicine.medical_specialty, endocrine system, Cell Adhesion/genetics, Macrophages/metabolism/pathology, 030209 endocrinology & metabolism, Inflammation, Hyperglycemia/genetics/metabolism/pathology, Biology, Islets of Langerhans, 03 medical and health sciences, Immune system, Von Willebrand factor, Diabetes mellitus, Internal medicine, Islets of Langerhans/immunology/metabolism/ pathology, Cell Adhesion, Internal Medicine, medicine, Animals, Rats, Wistar, 030304 developmental biology, geography, Macrophages, Gene Expression Profiling, Extracellular Matrix/metabolism, medicine.disease, Rats, Disease Models, Animal, Endocrinology, Diabetes Mellitus, Type 2, Hyperglycemia, biology.protein
Abstract: Article suite au 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes. 10-15 September 2005, Athens, Greece; International audience; The molecular pathways leading to islet fibrosis in diabetes are unknown. Therefore, we studied gene expression in islets of 4-month-old Goto-Kakizaki (GK) and Wistar control rats. Of 71 genes found to be overexpressed in GK islets, 24% belong to extracellular matrix (ECM)/cell adhesion and 34% to inflammatory/immune response families. Based on gene data, we selected several antibodies to study fibrosis development during progression of hyperglycemia by immunohistochemistry. One-month-old GK and Wistar islets appeared to be similar. Two-month-old GK islets were strongly heterogenous in terms of ECM accumulation compared with Wistar islets. GK islet vascularization, labeled by von Willebrand factor, was altered after 1 month of mild hyperglycemia. Numerous macrophages (major histocompatibility complex class II(+) and CD68(+)) and granulocytes were found in/around GK islets. These data demonstrate that marked inflammatory reaction accompanies GK islet fibrosis and suggest that islet alterations in this nonobese model of type 2 diabetes develop in a way reminiscent of microangiopathy.
Published: 2006
Full Text: View/download PDF

45. Inflammation and fibrosis on the Islets of Langerhans in the Goto-Kakizaki (GK) rat, spontaneous model of DT2: reflection of an insular microangiopathy?

Author: Homo-Delarche, Françoise, Calderari, Sophie, Irminger, J.C., Coulaud, J., Gangnerau, Marie-Noëlle, Rickenbach, K., Halban, Philippe, Portha, B., Serradas, Patricia, ProdInra, Migration, Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Département de médecine génétique et développement, Centre médical universitaire, and Société Francophone du Diabète (SFD). FRA.
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2006

46. Fatty acid signalling in the hypothalamus and the neural control of insulin secretion

Author: Migrenne, S., Cruciani-Guglielmacci, C., Kang, L., Wang, R., Rouch, C., Lefèvre, Al., Ktorza, A., Routh, Vh., Levin, Be., Magnan, Christophe, Laboratoire de physiopathologie de la nutrition (LPN), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
Published: 2006

47. roles physiologiques des endocannabinoides dans le controle de l'homéostasie énergétique

Author: Migrenne, S., Magnan, Christophe, Berthault, Marie France, Laboratoire de physiopathologie de la nutrition (LPN), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
Published: 2006

48. Is defective pancreatic beta-cell mass environmentally programmed in Goto-Kakizaki rat model of type 2 diabetes? Insights from crossbreeding studies during suckling period: Insights from crossbreeding studies during suckling period

Author: Bernard Portha, Marie-Noëlle Gangnerau, Patricia Serradas, Marie-José Meile, S. Calderari, Laboratoire de physiopathologie de la nutrition (LPN), and Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Blood Glucose, Male, Time Factors, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, 0302 clinical medicine, Endocrinology, Insulin-Secreting Cells, Homeostasis, Insulin, suckling, 2. Zero hunger, 0303 health sciences, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Animals, Suckling, 3. Good health, medicine.anatomical_structure, environmental programming, Female, Beta cell, Pancreas, gk rat, endocrine system, medicine.medical_specialty, Period (gene), Rat model, 030209 endocrinology & metabolism, Biology, Crossbreed, crossbreeding studies, Rats, Mutant Strains, 03 medical and health sciences, pancreatic beta cell mass, Internal medicine, Glucose Intolerance, Internal Medicine, medicine, Animals, Lactation, Endocrine system, Rats, Wistar, Pathological, 030304 developmental biology, type 2 diabete, Hepatology, Glucose Tolerance Test, medicine.disease, Rats, Disease Models, Animal, Glucose, Diabetes Mellitus, Type 2, Hybridization, Genetic, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The Goto-Kakizaki (GK) rat is a spontaneous model of type 2 diabetes with a well established pathological pancreatic beta-cell development. Hyperglycemia experienced during early postnatal life contributes to the programming of endocrine pancreas. We have analyzed the consequences of hyperglycemic versus euglycemic suckling period for the pancreatic beta-cell mass and the in vivo glucose tolerance and insulin secretion in 4-week-old unweaned control Wistar (W), diabetic GK, and in offspring issued from crosses between normoglycemic W and diabetic GK rats. Mother/father crosses yielded offspring designated as follows: W/W, GK/GK, W/GK, and GK/W. In vivo glucose tolerance and insulin secretion tests were performed on males 4 weeks after birth, that is, just before weaning. Beta-cell mass was determined by immunohistochemistry and morphometry. Four-week-old W/GK and GK/W rats are normoglycemic, normoinsulinemic, and display a similarly small beta-cell mass. Both W/GK and GK/W rats exhibit in vivo glucose intolerance and defective insulin secretion in response to glucose. Our data obtained from crossbreeding studies during suckling period suggest that the defective pancreatic beta-cell mass is not environmentally programmed in the GK model of type 2 diabetes. Rather, they support the hypothesis that the beta-cell mass defect in the GK is linked to genetic determinism.
Published: 2006
Full Text: View/download PDF

49. The effects of oleic-acid (OA) on distinct populations of neurons in the hypothalamic arcuate nucleus (ARC) are dependent on extracellular glucose levels

Author: Wang, R., Cruciani-Guglielmacci, C., Migrenne, S., Magnan, Christophe, Cotero, V., Routh, Vh., Laboratoire de physiopathologie de la nutrition (LPN), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
Published: 2006

50. Senseurs d'acide gras et controle nerveux de lhomé

Author: Cruciani-Guglielmacci, C., Migrenne, S., Clément, L., Magnan, Christophe, Laboratoire de physiopathologie de la nutrition (LPN), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and Berthault, Marie France
Published: 2006

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