Islet amyloid polypeptide tonally inhibits beta-, alpha-, and delta-cell secretion in isolated rat pancreatic islets

Islet amyloid polypeptide (LAPP, or amylin) is produced in pancreatic beta- cells. The intraislet significance of IAPP is still uncertain. In the prese nt study, paracrine effects of endogenous IAPP and somatostatin were invest igated in isolated rat pancreatic islets. The intraislet IAPP activity was inhibited with an IAPP antiserum or a specific antagonist [IAPP-(8-37)]. So matostatin activity was inhibited by immunoneutralization. Basal insulin an d glucagon secretion were not affected by the somatostatin and/or IAPP bloc kade. Arginine-stimulated insulin and glucagon secretion were dose dependen tly increased by IAPP antiserum, IAPP-(8-37), and somatostatin antiserum, r espectively. Arginine-stimulated samatostatin secretion was dose dependentl y potentiated by IAPP antiserum. Insulin secretion induced by 16.7 mill glu cose was enhanced by IAPP antiserum and IAPP-(8-37), respectively. A combin ation of somatostatin antiserum with IAPP antiserum or IAPP-(8-37) further enhanced the arginine-stimulated insulin and glucagon secretion compared wi th effects when the blocking reagents were used individually. These results indicate that endogenously produced LAPP tonally inhibits stimulated insul in, glucagon, and somatostatin secretion. Furthermore, the paracrine effect s of IAPP and somatostatin are additive.