ATP-sensitive potassium channels participate in glucose uptake in skeletal muscle and adipose tissue

1 Department of Cellular and Molecular Medicine, Graduate School of Medicine, 3 Research Center for Pathogenic Fungi and Microbial Toxicoses, and 5 Gene Research Center, Chiba University, Chiba 260-8670; 4 Department of Medical Biochemistry, Ehime University School of Medicine, Ehime 791-0295, Japan; and 2 Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada ATP-sensitive potassium (K ATP ) channels are known to be critical in the control of both insulin and glucagon secretion, the major hormones in the maintenance of glucose homeostasis. The involvement of K ATP channels in glucose uptake in the target tissues of insulin, however, is not known. We show here that Kir6.2( / ) mice lacking Kir6.2, the pore-forming subunit of these channels, have no K ATP channel activity in their skeletal muscles. A 2-deoxy-[ 3 H]glucose uptake experiment in vivo showed that the basal and insulin-stimulated glucose uptake in skeletal muscles and adipose tissues of Kir6.2( / ) mice is enhanced compared with that in wild-type (WT) mice. In addition, in vitro measurement of glucose uptake indicates that disruption of the channel increases the basal glucose uptake in Kir6.2( / ) extensor digitorum longus and the insulin-stimulated glucose uptake in Kir6.2( / ) soleus muscle. In contrast, glucose uptake in adipose tissue, measured in vitro, was similar in Kir6.2( / ) and WT mice, suggesting that the increase in glucose uptake in Kir6.2( / ) adipocytes is mediated by altered extracellular hormonal or neuronal signals altered by disruption of the K ATP channels. Kir6.2; SUR2; sulfonylurea; insulin; knockout mice