PACAP is an islet neuropeptide which contributes to glucose-stimulated insulin secretion

Pituitary adenylate cyclase activating peptide (PACAP) is a;ubiquitously di stributed neuropeptide which also is localized to pancreatic islets and sti mulates insulin secretion. We examined whether endogenous PACAP within,the islets might contribute to glucose-stimulated insulin secretion by immunone utralizing endogenous PACAP, Immunocytochemistry showed that PACAP immunore activity is expressed in nerve terminals within freshly isolated rat islets , but not in islets that had been cultured for 48 h. In contrast, islet end ocrine cells did not display PACAP immunoreactivity. :Addition of either of two specific PACAP antisera markedly inhibited glucose (11.1 mmol/l)-stimu lated insulin secretion from freshly isolated rat islets, whereas a control rabbit serum did not affect glucose-stimulated insulin secretion. In:contr ast, the PACAP antisera had no effect on glucose stimulated insulin secreti on in cultured islets. Based on these results we therefore suggest that PAC AP is an islet neuropeptide which is required for the normal insulinotropic action of glucose. (C) 1999 Academic Press.