2000 Fiscal Year Final Research Report Summary
A Role of ATP-Sensitive Potassium Channels in Glucose Transport into Cultured Human Skeletal Muscle Cells
| Project/Area Number |
11671138
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Diabetes Center, Tokyo Women's Medical University School of Medicine |
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Principal Investigator |
WASADA Taro Tokyo Women's Med. Univ. School of Med. Assoc. Prof., 医学部, 助教授 (70038850)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Chizuru Tokyo Women's Med. Univ. School of Med. Res. Fellow, 医学部, 助手 (90307497)
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| Project Period (FY) |
1999 – 2000
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| Keywords | ATP-sensitive potassium channel / K_<ATP> channel opener / blocker / Glucose transport / Human skeletal muscle cell / Protein kinase C / gliclazaide / PKC |
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| Research Abstract |
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.
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