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

ATP 敏感钾通道在葡萄糖转运至培养的人骨骼肌细胞中的作用

• 批准号: 11671138
• 负责人: WASADA Taro
• 金额: $ 2.24万
• 依托单位: Diabetes Center, Tokyo Women's Medical University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671138/
• 关键词: ATP-sensitive potassium channel; K_<ATP> channel opener; blocker; Glucose transport; Human skeletal muscle cell; Protein kinase C; gliclazaide; PKC

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.

多项证据表明ATP敏感性钾（K_<ATP>）通道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钾<ATP>通道活性对人骨骼肌细胞葡萄糖转运的影响。我们使用2-脱氧-D-^3H -葡萄糖或3-O-甲基-D-^3H-葡萄糖作为示踪剂，单独使用钾通道开放剂PCO-400和尼可地尔，或与通道阻断剂格列本脲和格列齐特联合使用，以检查它们对胰岛素或高葡萄糖浓度诱导的葡萄糖摄取的影响，PCO-400可抑制基底节细胞的增殖，葡萄糖浓度为5 mM时，2-DG或3-OMG的（非刺激）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，格列本脲或格列齐特可逆转其抑制作用。此外，PCO-400抑制高葡萄糖浓度促进的葡萄糖转运在没有胰岛素的情况下，这种作用也被两种磺酰脲类药物拮抗。关于钾通道<ATP>调节葡萄糖转运的机制，我们主要关注蛋白激酶C（PKC），因为PKC被认为参与胰岛素和高糖浓度刺激的葡萄糖转运。PMA（佛波醇12-肉豆蔻酸酯13-乙酸酯）剂量依赖性地逆转PCO-400诱导的胰岛素刺激的葡萄糖摄取抑制。在胰岛素或PMA存在下，抑制葡萄糖摄取的PCO-400对膜相关PKC活性无影响，提示K_<ATP>通道通过一种不依赖于PKC的机制调节骨骼肌基础和胰岛素依赖或非依赖的葡萄糖转运。

项目成果

Taro Wasada et al.: "ATP-Sensitive Potassium Channels Modulate Glucose Transport in Cultured Human Skeletal Muscle Cells"Endocrine Journal. (in press).

Taro Wasada 等人：“ATP 敏感钾通道调节培养的人类骨骼肌细胞中的葡萄糖转运”内分泌杂志。

T Wasada, C Watanabe, T Yano, M Ohta, N Yui, Y Iwamoto: "ATP-Sensitive Potassium Channels Modulate Glucose Transport in Cultured Human Skeletal Muscle Cells"Endocrine J. (in press).

T Wasada、C Watanabe、T Yano、M Ohta、N Yui、Y Iwamoto：“ATP 敏感钾通道调节培养的人类骨骼肌细胞中的葡萄糖转运”Endocrine J.（出版中）。

Wasada T et al.: "Adenosine triphosphate-sensitive potassium channels are involved in insulin-mediated glucose transport in humans"Metabolism. 48:4. 432-436 (1999)

Wasada T 等人：“三磷酸腺苷敏感钾通道参与人体胰岛素介导的葡萄糖转运”代谢。

Wasada T et al.: "Adenosine triphosphate-sensitive potassium channels are involved in insulin-mediated glucose transport in humans"Metabolism. 48. 432-436 (1999)

Wasada T 等人：“三磷酸腺苷敏感钾通道参与人体胰岛素介导的葡萄糖转运”代谢。

Wasada T, Watanabe C, Nakagami T, Iwamoto Y: "Adenosine triphosphate-sensitive potassium channels are involved in insulin-mediated glucose transport in humans."Metabolism. 48. 432-436 (1999)

Wasada T、Watanabe C、Nakagami T、Iwamoto Y：“三磷酸腺苷敏感钾通道参与人体胰岛素介导的葡萄糖转运。”代谢。