| Project/Area Number |
18K16241
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | インスリン感受性 / 糖尿病 / 細胞外マトリックス |
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| Outline of Final Research Achievements |
Fibulin5 (Fbln5), a matricellular secretory protein, is essential for the development of elastic fibers. We investigated the role of extracellular matrix on glucose metabolism using Fbln5 knockout(Fbln5KO) mice. Fbln5KO mice showed enhanced insulin sensitivity independent of body weight gain. In addition, Fbln5-deficiency protected mice against high-fat diet-induced obesity and fatty liver. We established tissue-specific Fbln5KO mice (hepatocyte, adipocyte, skin). However those mice did not showed altered insulin sensitivity compared with the control mice. In contrast, the intake of FITC-labeled insulin in the liver after administration via vena cava was increased in Fbln5KO mice. These results imply that Fbln5 regulate insulin sensitivity through vascular elastic fiver as well as a cell attachment.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では細胞外弾性線維関連分子によるインスリン感受性、エネルギー代謝制御機構について検討し組織周辺環境による代謝制御機構を提唱する。これまでインスリン感受性の責任臓器として、肝臓や骨格筋、脂肪組織などが代表と考えられてきたが、細胞外マトリックスによる制御については不明である。本研究により得られた知見は、メタボリックシンドロームの新たな分子機構の解明につながるものであり、糖尿病を始めとするメタボリックシンドロームの治療開発にも有用である。
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