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Neurotensin is a regulator of insulin secretion in pancreatic beta-cells
Authors:Sophie Béraud-Dufour  Amar Abderrahmani  Jacques Noel  Frédéric Brau  Gérard Waeber  Jean Mazella  Thierry Coppola
Affiliation:1. CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, 660 route des Lucioles, F-06560 Valbonne, France;2. Université de Nice Sophia Antipolis, F-06560, France;3. Service de Médecine interne, Centre Hospitalier Universitaire Vaudois-Université de Lausanne, Switzerland;4. Département de Biologie Cellulaire et de Morphologie, Université de Lausanne, Switzerland;1. College of Grassland Science, Key Laboratory of Grassland Ecosystem (Ministry of Education), Pratacultural Engineering Laboratory of Gansu Province, Sino-U. S. Centers for Grazing Land Ecosystem Sustainability, Gansu Agricultural University, Lanzhou 730070, PR China;2. Gansu Agricultural University-Massey University Research Centre for Grassland Biodiversity, Gansu Agricultural University, Lanzhou 730070, PR China;3. Institute of Natural and Mathematical Sciences, Massey University, Private Bag 102 904 North Shore Mail Centre 0632, Auckland, New Zealand;4. Ecological Genetics Laboratory, Landcare Research, Private Bag 92170, Auckland, New Zealand;5. Institute for Applied Ecology, University of Canberra, Bruce ACT 2601, Australia;3. From the Department of Cardiology and Protein Phosphorylation Research Group Lund University, SE 22184 Lund;4. Protein Phosphorylation Research Group Lund University, SE 22184 Lund;5. the Lund University Diabetes Centre, Lund University, SE 20502 Malmö, Sweden;1. Institute of Physiology, Pécs University, Medical School, Pécs, Hungary;2. Molecular Neuroendocrinology and Neurophysiology Research Group, Pécs University, Szentágothai Center, Pécs, Hungary;1. Cell Physiology Laboratory and Biomembrane Plasticity Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Republic of Korea;2. Department of Physiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Republic of Korea;3. Institute of Human-Environment Interface Biology, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Republic of Korea
Abstract:
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 PKCα and PKC? 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.
Keywords:
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