PACAP in the Glucose and Energy Homeostasis: Physiological Role and Therapeutic Potential

Pituitary adenylate cyclase activating polypeptide (PACAP) is a ubiquitous neuropeptide in the central and peripheral nervous systems. PACAP is also produced by pancreatic islet cells. PACAP regulates the glucose and energy metabolism at multiple processes in several tissues. At postprandial states, PACAP potentiates both insulin release from pancreatic β-cells and insulin action in adipocytes, contributing to energy storage. At fasting states, PACAP on the one hand promotes feeding behavior by activating neuropeptide Y neurons in the hypothalamic feeding center, arcuate nucleus, and on the other hand stimulates secretion of catecholamine and glucagon and thereby induces lipolysis in adipocytes and glucose output from liver. Thus, PACAP plays an integrative role in the glucose and energy homeostasis. Dysfunction of expression, secretion and/or action of PACAP might be involved in the type 2 diabetes and metabolic syndrome. PACAP receptor subtype-specific agonists and/or antagonists are hopeful therapeutic agents.