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

Abstract

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+ (KATP) channel in glucose homeostasis and, in particular, on its role in insulin secretion from pancreatic β-cells. The β-cell KATP 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 KATP channel structure and function, and consider how mutations in the KATP channel genes lead to neonatal diabetes or congenital hyperinsulinism.