2022 Fiscal Year Final Research Report
Regulation mechanisms of diacylglycerol kinase delta in differentiation and development of skeletal muscle to prevent exaggeration of type 2 diabetes
Project/Area Number |
20K07049
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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 |
Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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Research Institution | Shimane University |
Principal Investigator |
Sakai Hiromichi 島根大学, 学術研究院医学・看護学系, 助教 (00375255)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 2型糖尿病 / ジアシルグリセロールキナーゼ / 骨格筋 / 筋形成 / ミリスチン酸 |
Outline of Final Research Achievements |
Diacylglycerol kinase δ (DGKδ) positively regulates myogenic differentiation of C2C12 myoblasts, but the molecular mechanisms of its myogenesis and development into skeletal muscle are still unknown. In this study, we found that myristic acid, which upregulates DGKδ expression levels and glucose uptake in myotubes, increased DGKδ-dependently the expression levels of β-tubulin, one of important factors for muscle development, in C2C12 myotubes. Moreover, to investigate the development of skeletal muscle, we generated the skeletal muscle-specific DGKδ-knockout mice. The mice showed the approximately 10% reduction of body weight and skeletal muscle. In addition, brown adipocyte tissue was also decreased. In near future, we will reveal the roles of DGKδ on skeletal muscle and brown adipocyte tissue.
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Free Research Field |
脂質生化学
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Academic Significance and Societal Importance of the Research Achievements |
2型糖尿病(インスリン抵抗性)の改善のためには,食生活の乱れや運動不足により低下した骨格筋の機能(グルコース取り込み能)と量の回復が重要である.DGKδは骨格筋のグルコース取り込みに重要であり,一方で,DGKδが細胞レベルで筋分化誘導を正に制御する知見を得たが,筋形成における詳細な機構はわかっていなかった.今回,筋細胞のDGKδの発現を増加させるミリスチン酸がDGKδ発現依存的に筋形成に重要な役割を担うβ-tubulinの発現を増加させることを示した.この知見は,DGKδの発現増加は2型糖尿病患者で低下するグルコースの取り込み能と筋量の両方を改善する可能性を示している.
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