Insulinotropin PACAP potentiates insulin-stimulated glucose uptake in 3T3 L1 cells

Pituitary adenylate cyclase-activating polypeptide (PACAP) is localized in pancreatic nerve fibers and islets and potently augments glucose-induced insulin secretion. The present study explored a possible extra-pancreatic action of PACAP. The specific PACAP receptor (PAC, receptor) was expressed in the rat fat tissue and 3T3-L1 adipocytes. PACAP-38 (10 nM) significantly enhanced insulin-induced 2-deoxyglucose uptake by 3T3-L1 adipocytes. Insulin-stimulated phosphatidylinositol 3-kinase activity was further increased by PACAP-38, whereas the tyrosine-phosphorylation of insulin receptor beta-subunit and insulin receptor substrate-1 was unaltered by PACAP-38. These results reveal that PACAP-38 enhances insulin-induced glucose uptake. an effect probably mediated by insulin-stimulated phosphatidylinositol 3-kinase, and that PACAP potentiates not only insulin secretion, but also insulin action in adipocytes. (C) 1999 Elsevier Science Inc. All rights reserved.