| Project/Area Number |
16500412
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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 |
Sports science
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| Research Institution | Saga University |
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Principal Investigator |
HIGAKI Yasuki Saga University, Faculty of Medicine, Associate professor, 医学部, 助教授 (10228702)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | glucose transport / AMP kinase / insulin / Akt / oxidative stress / 骨格筋 / インスリン受容体 / PKB |
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| Research Abstract |
We determined the effects of oxidative stress on glucose uptake and intracellular signaling in skeletal muscle, a tissue continuously exposed to oxidative stress. Xanthine oxidase (XO) is a superoxide-generating enzyme that increases oxidative stress. Exposure of isolated rat extensor digitorum longus (EDL) muscles to hypoxanthine/XO (Hx/XO) resulted in a dose-dependent increase in glucose uptake. To determine if the mechanism leading to Hx/XO-stimulated glucose uptake is associated with the production of hydrogen peroxide (H_2O_2), EDL muscles from rats were preincubated with the H_2O_2 scavenger catalase prior to incubation with Hx/XO. Catalase treatment completely inhibited the increase in Hx/XO-stimulated 2-DG uptake, suggesting that H_2O_2 is an intermediary leading to Hx/XO-stimulated glucose uptake with incubation. Direct H_2O_2 also resulted in a dose-dependent increase in 2-DG uptake in isolated EDL muscles, and the maximal increase was threefold over basal levels at a concentration of 600 μmol/l H_2O_2. H_2O_2-stimulated 2-DG uptake was completely inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin, but not the nitric oxide inhibitor, N^G-monomethyl-L-arginine. H_2O_2 stimulated Akt Ser^<473> phosphorylation 7-fold above basal in isolated EDL muscles. H_2O_2 at 600 μmol/l had no effect on ATP concentrations and did not increase the activities of either the α 1 or α2 catalytic isoforms of AMP-activated protein kinase. These results demonstrate that oxidative stress is a potent stimulation of skeletal muscle glucose uptake and that this occurs through a phosphatidylinositol-3-kinase-dependent mechanism.
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