Expression of adenylyl cyclase subtypes in pancreatic beta-cells

Activation of adenylyl cyclase by Gs-coupled receptors for insulinotropic hormones such as glucagon-like peptide-1 and pituitary adenylate cyclase-activating polypeptide plays a critical role in stimulating glucose-induced insulin secretion. Despite this important role of insulinotropic hormones in the regulation of insulin secretion, little is known about which of the multiple subtypes of adenylyl cyclase are expressed in beta-cells. Here we report the use of PCR primers designed to amplify all subtypes of adenylyl cyclase from cDNA prepared from human and rat islets and from insulin-secreting beta-cell lines. PCR products were cloned and sequenced to identify the subtypes of adenylyl cyclase amplified. Adenylyl cyclase types V and VI, known to couple to Galphas and Gbetagamma in the cAMP signaling pathway, account for all subtypes identified in human islets and INS-1 cells and the majority of subtypes in rat islets and HIT-T15 cells. These findings indicate that pancreatic beta-cells are particularly well suited to transmit signals via Gs-coupled receptors such as that for glucagon-like peptide-1.