ATP-sensitive potassium channels participate in glucose uptake in skeletal muscle and adipose tissue.
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.
Miki
Takashi
T
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Research Center for Pathogenic Fungi and Microbial Toxicoses, and Gene Research Center, Chiba University, Chiba 260-8670, Japan.
Minami
Kohtaro
K
Zhang
Li
L
Morita
Mizuo
M
Gonoi
Tohru
T
Shiuchi
Tetsuya
T
Minokoshi
Yasuhiko
Y
Renaud
Jean-Marc
JM
Seino
Susumu
S
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D005215:Fasting / Q000378:metabolism; D005943:Gluconeogenesis / Q000502:physiology; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D006003:Glycogen; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose