9 results on '"Lupi, R"'
Search Results
2. The direct effects of GLP-1 and GIP, alone or in combination, on human pancreatic islets
- Author
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Lupi, R., Del Guerra, S., D'Aleo, V., Boggi, U., Filipponi, F., and Marchetti, P.
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B cell lymphoma , *ISLANDS of Langerhans , *TYPE 2 diabetes , *GLUCAGON-like peptide 1 , *GASTROINTESTINAL hormones , *PANCREATIC beta cells - Abstract
Abstract: GLP-1 and GIP are incretins known to affect beta-cell function and turnover. However, information on the direct actions of these hormones on human islet cells is limited. We tested the effects of acute (45min) or prolonged (2days) exposure to GLP-1 or GIP, alone or in combination, on the function and some molecular features of human islets isolated from non-diabetic and type 2 diabetic multiorgan donors. Acutely, both GLP-1 and, more markedly so, GIP, significantly potentiated glucose-stimulated insulin release, with no apparent synergic action. Some of these effects were observed with type 2 diabetic islets as well. Following prolonged exposure to the incretins, improved insulin secretion was observed, and transcription of insulin, PDX-1 and Bcl-2 was increased in both non-diabetic and diabetic islets, with the combination of GLP-1 and GIP showing more significant effects. Although it is still unclear at what extent these beta-cell direct actions of individual or combined incretins occur in-vivo in humans, nevertheless the results of the present study suggest that enhancing the exposure of pancreatic islets to circulating levels of both incretins may be useful for therapeutical purposes. [ABSTRACT FROM AUTHOR]
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- 2010
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3. Effects of exposure of human islet beta-cells to normal and high glucose levels with or without gliclazide or glibenclamide.
- Author
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Del Guerra, S., D’Aleo, V., Lupi, R., Masini, M., Bugliani, M., Boggi, U., Filipponi, F., and Marchetti, P.
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PANCREATIC beta cells ,ISLANDS of Langerhans ,GLICLAZIDE ,GLIBENCLAMIDE ,BODY mass index ,GLUCOSE ,CELL culture ,ELECTRON microscopy - Abstract
Copyright of Diabetes & Metabolism is the property of Masson Editeur and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2009
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4. Effects of exendin-4 on islets from type 2 diabetes patients.
- Author
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Lupi, R., Mancarella, R., Del Guerra, S., Bugliani, M., Del Prato, S., Boggi, U., Mosca, F., Filipponi, F., and Marchetti, P.
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PEOPLE with diabetes , *TYPE 2 diabetes , *CARBOHYDRATE intolerance , *PANCREATIC secretions , *PEPTIDES - Abstract
Exendin-4 is a dipeptidyl peptidase IV (DPP-IV)-resistant glucagon-like peptide1 (GLP-1) mimetic and its synthetic counterpart, exenatide, is being used in the therapy of type 2 diabetes (T2DM). No information, however, is currently available as for the direct action of exendin-4 on human T2DM islets. In the present study, we exposed pancreatic islets prepared from non-diabetic and T2DM subjects to exendin-4 for 48 h and found that the compound had several, direct beneficial actions on insulin secretion and the expression of genes involved in beta-cell function and differentiation. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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5. Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion.
- Author
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Ling, C., Del Guerra, S., Lupi, R., Rönn, T., Granhall, C., Luthman, H., Masiello, P., Marchetti, P., Groop, L., and Del Prato, S.
- Abstract
Insulin secretion in pancreatic islets is dependent upon mitochondrial function and production of ATP. The transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator-1 alpha (protein PGC-1α; gene PPARGC1A) is a master regulator of mitochondrial genes and its expression is decreased and related to impaired oxidative phosphorylation in muscle from patients with type 2 diabetes. Whether it plays a similar role in human pancreatic islets is not known. We therefore investigated if PPARGC1A expression is altered in islets from patients with type 2 diabetes and whether this expression is influenced by genetic ( PPARGC1A Gly482Ser polymorphism) and epigenetic (DNA methylation) factors. We also tested if experimental downregulation of PPARGC1A expression in human islets influenced insulin secretion. The PPARGC1A Gly482Ser polymorphism was genotyped in human pancreatic islets from 48 non-diabetic and 12 type 2 diabetic multi-organ donors and related to PPARGC1A mRNA expression. DNA methylation of the PPARGC1A promoter was analysed in pancreatic islets from ten type 2 diabetic and nine control donors. Isolated human islets were transfected with PPARGC1A silencing RNA (siRNA). PPARGC1A mRNA expression was reduced by 90% ( p < 0.005) and correlated with the reduction in insulin secretion in islets from patients with type 2 diabetes. After downregulation of PPARGC1A expression in human islets by siRNA, insulin secretion was reduced by 41% ( p ≤ 0. 01). We were able to ascribe reduced PPARGC1A expression in islets to both genetic and epigenetic factors, i.e. a common PPARGC1A Gly482Ser polymorphism was associated with reduced PPARGC1A mRNA expression ( p < 0.00005) and reduced insulin secretion ( p < 0.05). In support of an epigenetic influence, the PPARGC1A gene promoter showed a twofold increase in DNA methylation in diabetic islets compared with non-diabetic islets ( p < 0.04). We have shown for the first time that PPARGC1A might be important in human islet insulin secretion and that expression of PPARGC1A in human islets can be regulated by both genetic and epigenetic factors. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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6. Rosiglitazone prevents the impairment of human islet function induced by fatty acids: evidence for a role of PPARγ2 in the modulation of insulin secretion.
- Author
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Lupi, R., Del Guerra, S., Marselli, L., Bugliani, M., Boggi, U., Mosca, F., Marchetti, P., and Del Prato, S.
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PEROXISOMES , *NUCLEAR receptors (Biochemistry) , *ISLANDS of Langerhans , *COLLAGENASES , *DIGESTION , *FATTY acids , *GLUCOSE , *INSULIN - Abstract
Peroxisome proliferator-activated receptors (PPARs) are a subgroup of the superfamily of nuclear receptors, with three distinct main types: α, β and γ (subdivided into γ1 and γ2). Recently, the presence of PPARγ has been reported in human islets. Whether other PPAR types can be found in human islets, how islet PPARγ mRNA expression is regulated by the metabolic milieu, their role in insulin secretion, and the effects of a PPARγ agonist are not known. In this study, human pancreatic islets were prepared by collagenase digestion and density gradient purification from nonobese adult donors. The presence of PPAR mRNAs was assessed by RT-PCR, and the effect was evaluated of exposure for up to 24 h to either 22.2 mmol/1 glucose and/or 0.25, 0.5, or 1.0 mmol/1 long-chain fatty acid mixture (oleate to palmitate, 2:1). PPARβ and, to a greater extent, total PPARγ and PPARγ2 mRNAs were expressed in human islets, whereas PPARα mRNA was not detected. Compared with human adipose tissue, PPARγ mRNA was expressed at lower levels in the islets, and PPARβ at similar levels. The expression of PPARγ2 mRNA was not affected by exposure to 22.2 mmol/1 glucose, whereas it decreased markedly and time dependently after exposure to progressively higher free fatty acids (FFA). This latter effect was not affected by the concomitant presence of high glucose. Exposure to FFA caused inhibition of insulin mRNA expression, glucose-stimulated insulin release, and reduction of islet insulin content. The PPARγ agonists rosiglitazone and 15-deoxy-Δ-12,14prostaglandin J2 prevented the cytostatic effect of FFA as well as the FFA-induced changes of PPAR and insulin mRNA expression. In conclusion, this study shows that PPARγ mRNA is expressed in human pancreatic islets, with predominance of PPARγ2; exposure to FFA downregulates PPARγ2 and insulin mRNA expression and inhibits glucose-stimulated insulin secretion; exposure to PPARγ agonists can prevent these effects. [ABSTRACT FROM AUTHOR]
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- 2004
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7. Glucose transporter 2 gene polymorphisms and beta-cell function in isolated human pancreatic islets.
- Author
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Del Guerra, S., Lupi, R., D’Aleo, V., Filipponi, F., Boggi, U., and Marchetti, P.
- Published
- 2009
- Full Text
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8. Insulin secretion defects of human type 2 diabetic islets are corrected in vitro by a new reactive oxygen species scavenger
- Author
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Michela Novelli, R Mancarella, Ugo Boggi, S. Del Prato, Franco Mosca, Antonio Soleti, Piero Marchetti, Moreno Paolini, Gian Franco Pedulli, Franco Filipponi, Pellegrino Masiello, S Del Guerra, Luca Valgimigli, Roberto Lupi, Lupi R, Del Guerra S, Mancarella R, Novelli M, Valgimigli L, Pedulli GF, Paolini M, Soleti A, Filipponi F, Mosca F, Boggi U, Del Prato S, Masiello P, and Marchetti P.
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Type 2 diabetes ,medicine.disease_cause ,Antioxidants ,chemistry.chemical_compound ,Islets of Langerhans ,Endocrinology ,Internal medicine ,Diabetes mellitus ,Insulin Secretion ,Internal Medicine ,medicine ,Humans ,Insulin ,Cells, Cultured ,chemistry.chemical_classification ,Human pancreatic islet ,biology ,Nitrotyrosine ,Pancreatic islets ,Glutathione peroxidase ,Oxidative stress ,Antioxidant ,Insulin secretion ,General Medicine ,medicine.disease ,Oxidative Stress ,medicine.anatomical_structure ,Glucose ,chemistry ,Diabetes Mellitus, Type 2 ,Catalase ,biology.protein ,Tyrosine ,Reactive Oxygen Species - Abstract
Oxidative stress is a putative mechanism leading to beta-cell damage in type 2 diabetes. We studied isolated human pancreatic islets from type 2 diabetic and non-diabetic subjects, matched for age and body mass index. Evidence of increased oxidative stress in diabetic islets was demonstrated by measuring nitrotyrosine concentration and by electron paramagnetic resonance. This was accompanied by reduced glucose-stimulated insulin secretion, as compared to non-diabetic islets (Stimulation Index, SI: 0.9 +/- 0.2 vs. 2.0 +/- 0.4, P
- Published
- 2006
9. Activin A stimulates insulin secretion in cultured human pancreatic islets
- Author
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C. Falaschi, Ar Genazzani, Renzo Navalesi, L. Cobellis, Stefano Luisi, Roberto Lupi, Hiromu Sugino, Pasquale Florio, Felice Petraglia, Piero Marchetti, Florio, P, Luisi, S, Marchetti, P, Lupi, R, Cobellis, Luigi, Falaschi, C, Sugino, H, Navalesi, R, Genazzani, Ar, and Petraglia, F.
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endocrine system ,medicine.medical_specialty ,animal structures ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,activin A ,insulin ,human pancreatic islets ,glucose ,Paracrine signalling ,Islets of Langerhans ,Endocrinology ,Internal medicine ,Culture Techniques ,Insulin Secretion ,medicine ,Endocrine system ,Humans ,Insulin ,Inhibins ,Autocrine signalling ,Dose-Response Relationship, Drug ,Cell growth ,Chemistry ,Pancreatic islets ,medicine.disease ,Activins ,Gestational diabetes ,medicine.anatomical_structure ,Glucose ,embryonic structures ,Pancreas ,hormones, hormone substitutes, and hormone antagonists - Abstract
Activin A is a dimeric glycoprotein showing a high sequence homology with transforming growth factor-beta (TGF-beta) and playing autocrine/paracrine actions in reproductive tissues. However, since the synthesis of activin is ubiquitous it may have a role in regulating cell growth and differentiation in several tissues. Previous studies showed that activin A is expressed by insulin-positive B cells of human pancreatic islets, and women with gestational diabetes have higher serum activin A levels than healthy pregnant women at the same gestational age. The present study aimed to evaluate the effect of activin A on insulin secretion from cultured human pancreatic islets. With this purpose human pancreatic islets were incubated with varying concentrations of activin A (0.1 to 10.0 nM). In absence of glucose, activin A did not modify insulin secretion at the different concentrations used. In absence of activin A, 8.3 mM and 16.7 mM glucose significantly increased insulin secretion, with a dose-dependent pattern. In presence of a non stimulatory concentration of glucose (3.3 mM), activin A significantly increased insulin secretion starting from low concentration (0.1 nM). Furthermore, the addition of activin A to 8.3 mM and 16.7 mM glucose induced an additional effect of the dose-dependent glucose-mediated insulin secretion (p
- Published
- 2000
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