Role of pituitary adenylate cyclase-activating polypeptide in the pancreatic endocrine system.

Abstract:

:In the pancreatic islets, pituitary adenylate cyclase-activating polypeptide (PACAP) is expressed in beta cells and autonomic nerve terminals; the majority of these nerve terminals are parasympathetic. PACAP binds to three types of G protein-coupled receptors (GPCRs): VPAC1 receptors, VPAC2 receptors, and PAC1 receptors. All these receptor types are expressed in pancreatic islets. PACAP stimulates insulin and glucagon secretion. These actions are achieved in part through increased formation of cAMP after activation of adenylate cyclase and in part through increase in cytosolic calcium, achieved through increase in calcium uptake and release from intracellular calcium stores. Deletion of PAC1 receptors or VPAC2 receptors results in impaired insulin secretion and glucose intolerance. Studies in PAC1 receptor gene deleted mice have suggested that PACAP may be of physiological importance in mediating prandial insulin secretion and in contributing to the glucagon response to hypoglycemia. Animal studies have also suggested that activation of the receptors, in particular VPAC2 receptors, may be used as a therapeutic approach for the treatment of type 2 diabetes. Hence, PACAP is an islet neuropeptide with a potential role in islet physiology and as a basis for development of islet-promoting therapy in type 2 diabetes.

journal_name

Ann N Y Acad Sci

authors

Ahrén B

doi

10.1196/annals.1418.003

subject

Has Abstract

pub_date

2008-11-01 00:00:00

pages

28-35

eissn

0077-8923

issn

1749-6632

pii

NYAS1144003

journal_volume

1144

pub_type

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