Effects of islet amyloid polypeptide (amylin) and calcitonin gene-related peptide (CGRP) on glucose metabolism in the rat

In this study, we compared the effects of islet amyloid polypeptide (IAPP) and calcitonin gene-related peptide (CGRP) on glucose metabolism both in vivo and in vitro in the rat. Intravenous injection of rat CGRP caused a significant increase in plasma glucose concentration with a simultaneous increase in plasma insulin levels, whereas neither IAPP-NH 2 nor IAPP-COOH had any effect. Moreover, intravenous infusion of CGRP decreased tolerance to intragastric administration of glucose (O-GTT) without altering plasma insulin levels, but again IAPPs had no effect. On the other hand, 125I-[Tyr 0]rat CGRP specifically bound to the liver plasma membrane, and not only CGRP but also IAPP-NH 2 dose-dependently displaced the specific binding of 125I-[Tyr 0] CGRP, wherease IAPP-COOH had no effect. Conversely, CGRP as well as IAPP-NH 2 but not IAPP-COOH evoked dose-dependent activation of adenylate cyclase in the membranes, and these effects were significantly inhibited by a CGRP receptor antagonist, human CGRP-I(8-37). However, neither CGRP nor IAPP-NH 2 had any effect on glucose production in rat isolated hepatocytes. These results suggest that (1) IAPP-NH 2 but not IAPP-COOH induces adenylate cyclase activation via CGRP receptors on rat liver plasma membranes, and (2) CGRP might not involve its action on the liver in the changes of glucose metabolism.