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

Ashcroft FM. ATP-sensitive K channels and disease: from molecule to malady. Am J Physiol Endocrinol Metab 293: E880–E889, 2007. First published July 24, 2007; doi:10.1152/ajpendo.00348.2007.—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 -cells. The -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.