ATP-sensitive K+ channels and disease:: from molecule to malady

This essay is based on a lecture given to the American Physiological Society in honor of Walter B. Cannon, an advocate of homeostasis. It focuses on the role of the ATP-sensitive potassium K+ (K-ATP) channel in glucose homeostasis and, in particular, on its role in insulin secretion from pancreatic beta-cells. The beta-cell K-ATP channel comprises pore-forming Kir6.2 and regulatory SUR1 subunits, and mutations in either type of subunit can result in too little or too much insulin release. Here, I review the latest information on the relationship between K-ATP channel structure and function, and consider how mutations in the K-ATP channel genes lead to neonatal diabetes or congenital hyperinsulinism.