Calcitonin gene-related peptide (CGRP) and amylin and the endocrine pancreas

Abstract

Two newly discovered peptides, CGRP and amylin, have both been demonstrated to occur in the pancreas: CGRP in nerves and endocrine cells and amylin in insulin cells and the islet content of amylin insulin biosynthesis or degradation increase in diabetes. CGRP inhibits stimulated insulin secretion in normal experimental animals and in vitro, whereas amylin seems to lack such an effect, except in one study at a very high dose level. Both peptides seem to counteract the peripheral effects of insulin when investigated in vitro and in vivo. The studies summarized in this review have thus placed CGRP and amylin in the focus of intrapancreatic peptide research. The four main issues to address in further research within this field are now: (1) are CGRP and amylin secreted from the pancreas under normal conditions and in diabetes?, (2) do specific CGRP and/or amylin receptors occur in the islets?, (3) is CGRP involved in the physiological neural regulation of islet hormone secretion?, and (4) are CGRP and amylin involved in the pathogenesis of type 2 diabetes? All these issues offer great challenges to the groups involved not only in studies on effects and mechanisms of intrapancreatic peptides, but also in studies on the basic understanding of diabetes.