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Neuropeptides and the Regulation of Islet Function

From the Department of Clinical Sciences, Lund University, Lund, Sweden, and the Department of Experimental Medical Sciences, Lund University, Lund, Sweden

Address correspondence and reprint requests to Dr. Bo Ahrén, Department of Clinical Sciences, B11 BMC, SE-221 84 Lund, Sweden. E-mail: bo.ahren{at}med.lu.se

Abbreviations: CART, cocaine- and amphetamine-regulated transcript; CGRP, calcitonin gene–related polypeptide; GRP, gastrin-releasing polypeptide; GSIS, glucose-stimulated insulin secretion; NPY, neuropeptide Y; PACAP, pituitary adenylate cyclase–activating polypeptide; PP, pancreatic polypeptide; TH, tyrosine hydroxylase; VIP, vasoactive intestinal polypeptide

The pancreatic islets are richly innervated by autonomic nerves. The islet parasympathetic nerves emanate from intrapancreatic ganglia, which are controlled by preganglionic vagal nerves. The islet sympathetic nerves are postganglionic with the nerve cell bodies located in ganglia outside the pancreas. The sensory nerves originate from dorsal root ganglia near the spinal cord. Inside the islets, nerve terminals run close to the endocrine cells. In addition to the classic neurotransmitters acetylcholine and norepinephrine, several neuropeptides exist in the islet nerve terminals. These neuropeptides are vasoactive intestinal polypeptide, pituitary adenylate cyclase–activating polypeptide, gastrin-releasing polypeptide, and cocaine- and amphetamine-regulated transcript in parasympathetic nerves; neuropeptide Y and galanin in the sympathetic nerves; and calcitonin gene–related polypeptide in sensory nerves. Activation of the parasympathetic nerves and administration of their neurotransmitters stimulate insulin and glucagon secretion, whereas activation of the sympathetic nerves and administration of their neurotransmitters inhibit insulin but stimulate glucagon secretion. The autonomic nerves contribute to the cephalic phase of insulin secretion, to glucagon secretion during hypoglycemia, to pancreatic polypeptide secretion, and to the inhibition of insulin secretion, which is seen during stress. In rodent models of diabetes, the number of islet autonomic nerves is upregulated. This review focuses on neural regulation of islet function, with emphasis on the neuropeptides.

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