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Diabetes 53:S176-S180, 2004
© 2004 by the American Diabetes Association, Inc.

Section IV: Non-Beta-Cell ATP-Sensitive K+ Channels

Roles of ATP-Sensitive K+ Channels as Metabolic Sensors

Studies of Kir6.x Null Mice

Kohtaro Minami1, Takashi Miki2, Takashi Kadowaki3, and Susumu Seino1,2

1 Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kobe, Japan
2 Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
3 Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

ATP-sensitive K+ channels (KATP channels) are present in various tissues, including pancreatic ß-cells, heart, skeletal muscles, vascular smooth muscles, and brain. KATP channels are hetero-octameric proteins composed of inwardly rectifying K+ channel (Kir6.x) and sulfonylurea receptor (SUR) subunits. Different combinations of Kir6.x and SUR subunits comprise KATP channels with distinct electrophysiological and pharmacological properties. Recent studies of genetically engineered mice have provided insight into the physiological and pathophysiological roles of Kir6.x-containing KATP channels. Analysis of Kir6.2 null mice has shown that Kir6.2/SUR1 channels in pancreatic ß-cells and the hypothalamus are essential in glucose-induced insulin secretion and hypoglycemia-induced glucagon secretion, respectively, and that Kir6.2/SUR2 channels are involved in glucose uptake in skeletal muscles. Kir6.2-containing KATP channels in brain also are involved in protection from hypoxia-induced generalized seizure. In cardiovascular tissues, Kir6.1-containing KATP channels are involved in regulation of vascular tonus. In addition, the Kir6.1 null mouse is a model of Prinzmetal angina in humans. Our studies of Kir6.2 null and Kir6.1 null mice reveal that KATP channels are critical metabolic sensors in acute metabolic changes, including hyperglycemia, hypoglycemia, ischemia, and hypoxia.

Address correspondence and reprint requests to Susumu Seino, MD, DMSc, Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. E-mail: seino{at}med.kobe-u.ac.jp


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.