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

ATP-sensitive potassium (KATP) 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 KATPchannels 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 KATPchannel activity in their skeletal muscles. A 2-deoxy-[3H]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...