Neurotensin is a regulator of insulin secretion in pancreatic beta-cells.
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.
Béraud-Dufour
Sophie
S
CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
Abderrahmani
Amar
A
Noel
Jacques
J
Brau
Frédéric
F
Waeber
Gérard
G
Mazella
Jean
J
Coppola
Thierry
T
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection; D004789:Enzyme Activation / Q000187:drug effects; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009496:Neurotensin / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D018028:Receptors, Neurotensin / Q000819:agonists
D007328:Insulin; D010880:Piperidines; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C079087:SR 48692; D009496:Neurotensin; D017868:Cyclic AMP-Dependent Protein Kinases; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; C047340:levocabastine