| Project/Area Number |
16K09744
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
今村 武史 鳥取大学, 医学部, 教授 (00552093)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 骨格筋 / AMPK / 糖代謝 / 加齢 / 肥満 / ミトコンドリア / 脂質代謝 / 糖鎖修飾 / O-GlcNAc / AMPキナーゼ / 翻訳後修飾 / 糖鎖 / 糖尿病 / 生理学 / シグナル伝達 / 老化 |
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| Outline of Final Research Achievements |
O-GlcNAcylation is a post-translational modification that is characterized by the addition of N-acetylglucosamine(GlcNAc) to proteins by O-GlcNAc transferase (Ogt). The degree of O-GlcNAcylation is thought to be associated with glucotoxicity and diabetic complications, because GlcNAc is produced by a branch of the glycolytic pathway. However, its role in skeletal muscle has not been fully elucidated. In this study, we created skeletal muscle-specific Ogt knockout (Ogt-MKO) mice and analyzed their glucose metabolism. During an intraperitoneal glucose tolerance test, blood glucose was slightly lower in Ogt-MKO mice than in control Ogt-flox mice. High fat diet-induced obesity and insulin resistance were reversed in Ogt-MKO mice. In addition, 12-month-old Ogt-MKO mice had lower body mass with increased AMP-activated protein kinase a (AMPKa) protein expression. In conclusion, loss of O-GlcNAcylation facilitates glucose utilization in skeletal muscle, potentially through AMPK activation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究結果より、O-GlcNAc修飾が骨格筋で起こらなくなると、血糖が低下し、体重が減少する事が分かった。Ogtノックアウトマウスは少なくとも1歳を超えて元気に過ごしており、目立った臓器障害も観察されなかったことから、糖尿病や肥満の新規治療ターゲットになる可能性がある。しかしながら、他の研究で脂肪細胞や膵β細胞でO-GlcNAc修飾がなくなると臓器障害を来して言うことから、骨格筋だけに薬剤が吸収されるようなドラッグデリバリー技術との組み合わせが必要となると考えられる。
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