A Role of ATP-Sensitive Potassium Channels in Glucose Transport into Cultured Human Skeletal Muscle Cells

一些证据表明，ATP敏感的钾通道（K_<ATP>）参与胰岛素靶组织的葡萄糖摄取。本研究的目的是直接证明K_<ATP>通道活性对葡萄糖转运到培养的人骨骼肌细胞的影响。我们分别以2-脱氧d -^3H-葡萄糖或3- o -甲基d -^3H-葡萄糖为示踪剂，使用钾通道打开剂PCO-400和尼可地尔单独或与通道阻滞剂格列本脲和格列齐特联合检测它们对胰岛素或高葡萄糖诱导的葡萄糖摄取的影响。在葡萄糖浓度为5mm时，PCO-400抑制基础（非刺激）2-DG或3-OMG的摄取。PCO-400和尼可地尔剂量依赖性地抑制胰岛素刺激的葡萄糖摄取，其抑制作用被格列本脲或格列齐特逆转。此外，在缺乏胰岛素的情况下，PCO-400抑制高浓度葡萄糖促进的葡萄糖转运，这种作用也被两种磺脲类药物拮抗。关于K_<ATP>通道调节葡萄糖转运的机制，我们关注的是蛋白激酶C (PKC)，因为PKC被认为参与胰岛素和高浓度葡萄糖刺激的葡萄糖转运。PMA （phorbol 12-肉豆蔻酸酯13-乙酸酯）剂量依赖性地逆转了pco -400诱导的胰岛素刺激的葡萄糖摄取抑制。另一方面，抑制葡萄糖摄取浓度的PCO-400在胰岛素或PMA存在下不会引起膜相关PKC活性的改变。从这些结果我们得出结论，K_<ATP>通道通过独立于PKC的机制调节骨骼肌中基础的、胰岛素依赖的或独立的葡萄糖运输。

Several lines of evidence suggest that ATP-sensitive potassium (K_<ATP>) channels are involved in glucose uptake by insulin target tissues. The aim of the present study was to prove directly the effect of K_<ATP> channel activity on glucose transport into cultured human skeletal muscle cells. We used potassium channel openers PCO-400 and nicorandil alone or in combination with channel blockers glibenclamide and gliclazide to examine their effects on insulin- or high glucose concentration-induced glucose uptake using 2-deoxy-D-^3H -glucose or 3-O-methyl-D-^3H-glucose as tracer, respectively.PCO-400 inhibited the basal (non-stimulated) uptake of 2-DG or 3-OMG at the glucose concentration of 5 mM.PCO-400 and nicorandil dose-dependently inhibited insulin-stimulated glucose uptake, and their inhibitory effects were reversed by glibenclamide or gliclazide. In addition, PCO-400 inhibited high glucose concentration-facilitated glucose transport in the absence of insulin, and this effect was also antagonized by both sulfonylurea drugs. Regarding a mechanism by which K_<ATP> channels modulate glucose transport, we focused on protein kinase C (PKC), because PKC has been supposed to participate in both insulin- and high glucose concentration-stimulated glucose transport. PMA (phorbol 12-myristate 13-acetate) dose-dependently reversed the PCO-400-induced suppression of insulin-stimulated glucose uptake. On the other hand, PCO-400 at the concentration that inhibited glucose uptake caused no alteration of membrane-associated PKC activity in the presence of insulin or PMA.From these results we conclude that K_<ATP> channels modulate the basal and insulin-dependent or independent glucose transport in skeletal muscle through a mechanism independent of PKC.