The role of O-GlcNAcylation in the Glucose metabolism in Skeletal Muscle
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 |
Section | 一般 |
Research Field |
Metabolomics
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Research Institution | Shiga University of Medical Science |
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 |
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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Report
(4 results)
Research Products
(10 results)
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[Presentation] Lack of O-GlcNAcylation Enhances Exercise-Dependent Glucose Utilization through Amp Kinase Activation in Skeletal Muscle2017
Author(s)
KOICHIRO MURATA, KATSUTARO MORINO, SHOGO IDA, NATSUKO OHASHI, HIROTAKA IWASAKI, MENGISTU LEMECHA SHUKARE, OSAMU SEKINE, SHINJI KUME, SHI YOUNG PARK, CHEOL SOO CHOI, SATOSHI UGI, HIROSHI MAEGAWA
Organizer
American Diabetes Association 77th
Related Report
Int'l Joint Research
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[Presentation] Comprehensive Analysis to Reveal Physiological Role of O-GlcNAcylation in Glucose Metabolism by Using Tissue-Specific Ogt Knockout Mice2017
Author(s)
SHOGO IDA, KATSUTARO MORINO, OSAMU SEKINE, NATSUKO OHASHI, SHINJI KUME, KANAKO IWASAKI, NORIO HARADA, NOBUYA INAGAKI, SATOSHI UGI, HIROSHI MAEGAWA,
Organizer
American Diabetes Association 77th
Related Report
Int'l Joint Research