Modification of Exercise-Stimulated AMP Kinase Activity and Its Physiological Function in Skeletal Muscle.
| Project/Area Number |
17500424
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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 | Kyoto University |
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Principal Investigator |
HAYASHI Tatsuya Kyoto University, Graduate School of Human & Environmental Studies, Associate Professor, 大学院人間・環境学研究科, 准教授 (00314211)
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| Co-Investigator(Kenkyū-buntansha) |
FUSHIKI Tohru Kyoto University, Graduate School of Agriculture, Professor, 大学院農学研究科, 教授 (20135544)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | skeletal muscle / exercise / insulin sensitivity / AMP kinase / muscle contraction / signal transduction / glucose metabolism / melanocortin / 糖輸送担体 / 高脂肪食 |
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| Research Abstract |
We activated rodent muscle AMPK activity to a level comparable to that achieved by physiological exercise or tetanic contraction by pharmacological AMPK stimulator, 5-aminoimidazole-4-carboxamide-1-β-_D-ribonucleoside (AICAR). Similar to a single bout of swimming, a single intraperitoneal or subcutaneous injection of AICAR led to an acute increase in insulin-independent glucose transport (GT), and similar to exercise training, repeated injection increased GLUT4 protein and insulin-dependent GT in mouse muscle. We also used an isolated rat muscle preparation and activated AMPK with contraction or AICAR in vitro, with a corresponding increase in GT. Whereas contraction stimulated glycogen synthase (GS), AICAR decreased GS activity. Whereas contraction activated glycogen phosphorylase (GP), AICAR did not alter GP activity. The muscle glycogen content decreased in response to contraction but was unchanged by AICAR. Lactate release was increased when muscles were stimulated with AICAR in bu
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ffer containing glucose, indicating that the glucose taken up into the muscle was catabolized via glycolysis. These results suggest that (1) exercise promotes GT, GLUT4 expression and insulin sensitivity via activation of AMPK, (2) AMPK does not mediate contraction-stimulated glycogen synthesis or glycogenolysis, and (3) acute AMPK activation leads to an increased glycolytic flux by antagonizing contraction-stimulated glycogen synthesis. We also investigated the role of the central nervous system in the control of muscle metabolism. We treated mice intracerebroventricularly with a melanocortin agonist MT-II or antagonist SHU9119. MT-II augmented phosphorylation of AMPK while AMPK phosphorylation by leptin was abrogated by SHU9119 or in KKA^y mice, which centrally express endogenous melanocortin antagonist. Importantly, diet-induced attenuation of AMPK phosphorylation in leptin-overexpressing transgenic mice was not reversed by central leptin but was markedly restored by MT-II. Our data provide evidence for the critical role of the melanocortin system in the leptin-skeletal muscle AMPK axis and highlight the possible relevance of CNS regulation of muscle AMK during exercise. Less
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Report
(3 results)
Research Products
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