Abstract
The pharmacological roles of the neuropeptide neurotensin through its three known receptors are various and complex. Neurotensin is involved in several important biological functions including analgesia and hypothermia in the central nervous system and also food intake and glucose homeostasis in the periphery. This review focuses on recent works dealing with molecular mechanisms regulating blood glucose level and insulin secretion upon neurotensin action. Investigations on crucial cellular components involved in the protective effect of the peptide on beta cells are also detailed. The role of xenin, a neurotensin-related peptide, on the regulation of insulin release by glucose-dependent insulinotropic polypeptide is summarized. The last section comments on the future research areas which should be developed to address the function of new effectors of the neurotensinergic system in the endocrine pancreas.
Highlights
The endogenous peptide neurotensin (NT) was discovered in 1973 in bovine hypothalami by Carraway and Leeman (1973) for its ability to induce vasodilatation
From the overall data obtained on pancreatic beta cells and islets, it is clear that the three NT receptors are expressed, the effects of NT involve both NTSR2 and NTSR3/sortilin but not NTSR1 (Figure 1)
This is intriguing since the majority of the actions of NT both in the brain and in the periphery involves, at least partly, NTSR1, a receptor which was always shown to be expressed and functional at the plasma membrane of NT target cells
Summary
Jean Mazella*, Sophie Béraud-Dufour, Christelle Devader, Fabienne Massa and Thierry Coppola*. Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Centre National de la Recherche Scientifique, Université de Nice-Sophia Antipolis, Valbonne, France. Reviewed by: Isabelle Dubuc, Université de Rouen, France Gina Leinninger, Michigan State University, USA. The pharmacological roles of the neuropeptide neurotensin through its three known receptors are various and complex. Neurotensin is involved in several important biological functions including analgesia and hypothermia in the central nervous system and food intake and glucose homeostasis in the periphery. This review focuses on recent works dealing with molecular mechanisms regulating blood glucose level and insulin secretion upon neurotensin action. Investigations on crucial cellular components involved in the protective effect of the peptide on beta cells are detailed. The role of xenin, a neurotensin-related peptide, on the regulation of insulin release by glucose-dependent insulinotropic polypeptide is summarized.
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