Neuropeptides and Insulin Secretion

Abstract

AbstractThe pancreatic islets are richly innervated by parasympathetic, sympathetic, and, sensory nerves and these nerves have been shown to be of importance for the regulation of islet function. The terminals of the islet autonomic nerves harbor, however, not only the classical neurotransmitters, acetylcholine and noradrenaline, but also several neuropeptides. These neuropeptides are vasoactive intestinal polypeptide (VIP), pituitary adenlyate cyclase activating polypeptide (PACAP), and gastrin releasing peptide (GRP) in the parasympathetic nerve terminals; galanin and neuropeptide Y (NPY) in the sympathetic nerve terminals; and calcitonin gene‐related peptide (CGRP) and substance P (SP) in the sensory nerves. These neuropeptides may mediate activation of the autonomic nerves on islet hormone secretion. Thus, insulin secretion stimulated by parasympathetic nerves may be mediated by VIP, PACAP, and GRP, which all stimulate insulin secretion, whereas inhibition of insulin secretion by sympathetic nerve activation may be mediated by galanin and NPY, which both inhibit insulin secretion. The neuropeptides in the sensory nerve terminals—CGRP and SP—inhibit insulin secretion.The actions of the neurotransmitters on insulin secretion are elicited by different receptors affecting different signaling pathways in the β‐cells. For example, VIP and PACAP activate adenylate cyclase and GRP activates phospholipase C, whereas galanin and NPY inhibit adenylate cyclase. In addition, the neurotransmitters affect ionic channel activity and exert direct influences on the exocytosis machinery.The islet autonomic nerves seem to be of physiological importance for insulin secretion in various conditions. Thus, parasympathetic nerves mediate the cephalic phase of insulin secretion after a meal intake and synchronize the islets to function as a unit, allowing oscillations of islet hormone secretion. The sympathetic nerves optimize islet hormone secretion during metabolic stress or physical activity. The autonomic nerves might also be involved in the islet adaptation to insulin resistance with possible implication for the development of glucose intolerance and type 2 diabetes.The islet innervation is thus of importance both for the physiology and pathophysiology of the islets through contribution by all branches of the autonomic nerves and several different neurotransmitters.