Expression of adenylyl cyclase subtypes in pancreatic beta-cells

Activation of adenylyl cyclase by G(s)-coupled receptors for insulinotropic hormones such as glucagon-like peptide-1 and pituitary adenylate cyclase-a ctivating polypeptide plays a critical role in stimulating glucose-induced insulin secretion. Despite this important role of insulinotropic hormones i n the regulation of insulin secretion, little is known about which of the m ultiple subtypes of adenylyl cyclase are expressed in beta-cells. Here we r eport the use of PCR primers designed to amplify all subtypes of adenylyl c yclase from cDNA prepared from human and rat islets and from insulin-secret ing beta-cell lines. PCR products were cloned and sequenced to identify the subtypes of adenylyl cyclase amplified. Adenylyl cyclase types V and VI, k nown to couple to G alpha(s) and G beta gamma in the cAMP signaling pathway , account for all subtypes identified in human islets and INS-1 cells and t he majority of subtypes in rat islets and HIT-T15 cells, These findings ind icate that pancreatic beta-cells are particularly well suited to transmit s ignals via G(s)-coupled receptors such as that for glucagon-like peptide-1. (C) 1999 Academic Press.