Inhibitory action of islet amyloid polypeptide and calcitonin gene-related peptide on release of insulin from the isolated perfused rat pancreas.

Islet (or insulinoma) amyloid polypeptide (IAPP) is a 37-residue peptide recently purified from amyloid deposits in the pancreas of patients with type 2 diabetes and from amyloid deposits of a human insulinoma. IAPP immunoreactivity has been identified in islet B cells of diabetic and nondiabetic humans. IAPP is structurally similar to calcitonin gene-related peptide (CGRP). The purpose of this study was to examine the effects of IAPP and CGRP on glucose- and carbachol-stimulated release of insulin and pancreatic polypeptide (PP) from the isolated perfused rat pancreas. IAPP and CGRP, at 10(-7) M, failed to inhibit glucose-stimulated (16.7 mM) release of insulin. At the same concentration, however, IAPP significantly (p less than 0.05) inhibited carbachol-stimulated (10(-7) M) release of insulin by 30%, and CGRP significantly inhibited carbachol-stimulated release of insulin by 33% when compared with the control group. IAPP also significantly decreased carbachol-stimulated release release of PP. IAPP and CGRP, at 10(-8) M, did not inhibit carbachol-stimulated release of insulin and PP. These results suggest that IAPP and CGRP may have roles in the regulation of secretion of insulin. IAPP may inhibit secretion of insulin, at least in part, by blocking cholinergic mechanisms.