Islet amyloid polypeptide regulates multiple steps in stimulus-secretion coupling of beta cells in rat pancreatic islets

Islet amyloid polypeptide (IAPP) is produced in pancreatic beta cells. Intr aislet function of IAPP is still uncertain. In the present study, we invest igated effects of IAPP and somatostatin on stimulus-secretion coupling of b eta cells in isolated rat pancreatic islets, Insulin secretion induced by 2 2.2 mM glucose was increased by an IAPP antiserum (0.1%) or an IAPP antagon ist (IAPP8-37, 10 mu M). Pretreatment of islets with per tussis toxin (PTX) abolished the stimulating effect of IAPP8-37 on glucose-induced insulin se cretion. In contrast, IAPP antiserum and IAPP8-37 did not change insulin se cretion induced by 30 mM KCl. Somatostatin (1 nM) inhibited insulin secreti on induced by 22.2 mM glucose, 10 mM L-arginine, 25 mu M forskolin, and 200 mu M carbachol. IAPP (10 mu M) enhanced the inhibitory effect of somatosta tin on insulin secretion induced by L-arginine or forskolin. PTX pretreatme nt abolished the effects of somatostatin and IAPP on arginine-induced insul in secretion. In conclusion, IAPP regulates multiple steps in signal transd uctions of beta cells. The effects of IAPP on beta cells are mediated by PT X-sensitive regulatory G proteins.