Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a ubiquitous neuropeptide in the central and peripheral nervous systems. Previously we reported that PACAP potentiates both insulin release from pancreatic β-cells and insulin action in adipocytes, contributing to reduction of blood glucose and energy storage. PACAP38 is localized in pancreatic islets and serves as an endogenous amplifier of glucose-induced insulin secretion via VPAC2 and PAC1 subtypes of PACAP receptors. In an adipocyte cell-line, 3T3-L1 cells, PACAP enhances insulin-stimulated glucose uptake via PAC1 receptors and promotes adipocyte differentiation. In contrast, PACAP stimulates secretion of glucagon and catecholamine and glucose output from the liver, causing elevation of blood glucose. Thus, PACAP regulates the glucose and energy metabolism at multiple processes in several tissues. In this symposium, we present three novel effects of PACAP in the metabolism. (1) The action of PACAP to protect islet cells against lipotoxicity and glucotoxicity. (2) PACAP knock out mice exhibits decreased fat mass and increased insulin sensitivity, suggesting a role of PACAP to facilitate adiposity and decrease insulin sensitivity. (3) PACAP promotes feeding behavior by activating neuropeptide Y neurons in the hypothalamic arcuate nucleus, a feeding center.Based on these well known and newly identified metabolic effects of PACAP, we discuss a possible therapeutic use of PACAP receptor subtype-specific agonists and/or antagonists in the treatment of metabolic syndrome. [J Physiol Sci. 2006;56 Suppl:S56]
