1. Neurotensin is a regulator of insulin secretion in pancreatic beta-cells
- Author
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Gérard Waeber, Thierry Coppola, Amar Abderrahmani, Jacques Noël, Jean Mazella, Frédéric Brau, Sophie Béraud-Dufour, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Département de Médecine Interne, Université de Lausanne (UNIL), and Département de Biologie Cellulaire et de Morphologie
- Subjects
medicine.medical_treatment ,MESH: Neurotensin ,Biochemistry ,MESH: Insulin-Secreting Cells ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,Insulin-Secreting Cells ,Insulin Secretion ,Insulin ,Receptors, Neurotensin ,MESH: Animals ,PKC ,Neurotensin ,Calcium signaling ,0303 health sciences ,MESH: Protein Kinase C-epsilon ,Insulin oscillation ,MESH: Piperidines ,medicine.anatomical_structure ,Quinolines ,MESH: Protein Kinase C-alpha ,Beta cell ,MESH: Quinolines ,MESH: Enzyme Activation ,medicine.medical_specialty ,Protein Kinase C-alpha ,MESH: Rats ,chemistry.chemical_element ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,MESH: Cyclic AMP-Dependent Protein Kinases ,MESH: Insulin ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Protein Kinase C-epsilon ,Biology ,Calcium ,MESH: Calcium Signaling ,Cell Line ,Pancreatic islet ,MESH: Receptors, Neurotensin ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Calcium Signaling ,030304 developmental biology ,Calcium metabolism ,Pancreatic islets ,Cell Biology ,Cyclic AMP-Dependent Protein Kinases ,MESH: Cell Line ,Rats ,Enzyme Activation ,MESH: Cytoprotection ,Endocrinology ,chemistry ,Cytoprotection ,Pyrazoles ,MESH: Pyrazoles ,030217 neurology & neurosurgery - Abstract
International audience; Neurotensin (NT) is secreted from neurons and gastrointestinal endocrine cells. We previously reported that the three NT receptors (NTSRs) are expressed in pancreatic islets and beta cell lines on which we observed a protective effect of NT against cytotoxic agents. In this study, we explored the role of NT on insulin secretion in the endocrine pancreatic beta cells. We observed that NT stimulates insulin secretion at low glucose level and has a small inhibiting effect on stimulated insulin secretion from isolated islets or INS-1E cells. We studied the mechanisms by which NT elicited calcium concentration changes using fura-2 loaded islets or INS-1E cells. NT increases calcium influx through the opening of cationic channels. Similar calcium influxes were observed after treatment with NTSR selective ligands. NT-evoked calcium regulation involves PKC and the translocation of PKCalpha and PKCepsilon to the plasma membrane. Part of NT effects appears to be also mediated by PKA but not via the Erk pathway. Taken together, these data provide evidence for an important endocrine role of NT in the regulation of the secretory function of beta cells.
- Published
- 2010
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