2023 Fiscal Year Final Research Report
Study on the mechanism of diabetic muscle atrophy
| Project/Area Number |
22K19734
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
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| Research Institution | Tokyo Metropolitan University |
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Principal Investigator |
Manabe Yasuko 東京都立大学, 人間健康科学研究科, 准教授 (60467412)
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| Co-Investigator(Kenkyū-buntansha) |
田岡 万悟 東京都立大学, 理学研究科, 准教授 (60271160)
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| Project Period (FY) |
2022-06-30 – 2024-03-31
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| Keywords | skeletal muscle / contraction / muscle atrophy / diabetes |
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| Outline of Final Research Achievements |
Diabetes induces significant muscle atrophy via an unknown mechanism. We found that the myotubes treated with diabetic mice serum weakened muscle contractile force, indicating that some factors in the diabetic serum induce muscle atrophy.
To investigate the biochemical properties of the factors in diabetic serum that induce muscle atrophy, myotubes were administered by the heat-treated diabetic serum and measured the contractile force. As a result, the heat-treated diabetic serum lost the ability to induce muscle atrophy. To determine whether the target molecules in the diabetic serum that induce muscle atrophy are protein, the serum was treated by protease K, a serine protease. Unexpectedly, the diabetes serum treated by the protease further enhanced muscle atrophy compared to untreated diabetes serum. These results suggest that the factors in the diabetes serum that induce muscle atrophy are proteins whose activity is enhanced by serine proteases.
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| Free Research Field |
運動分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では糖尿病患者では筋萎縮が生じるリスクが上昇するという現象を明らかにするために、糖尿病マウスの血清中の分子が筋萎縮に関与するかを検証した。糖尿病マウスの血清を処理した筋細胞では、ミオシン重鎖Iの有意な低下、および収縮力の有意な減少が観察された。筋細胞モデルで糖尿病性筋萎縮の特徴を再現できたことは、今後の筋萎縮研究の有用なモデルとして意義は大きい。また、萎縮を誘導する分子はセリンプロテアーゼによって萎縮活性が増加するタンパク質性分子であること明らかになった。今後、さらに研究をすすめ、萎縮を誘導する血中の分子を同定することで、糖尿病性筋萎縮の原因解明および治療薬開発に寄与できる。
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