| Project/Area Number |
18K08463
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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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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Gunma University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | インスリン作用 / グルコーストランスポーター / 活性酸素 / 脂肪細胞 / NADPHオキシダーゼ / 小胞輸送 / タンパク質寿命 / タンパク寿命 / インスリン / GLUT4 / 過酸化水素 |
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| Outline of Final Research Achievements |
Our previous studies revealed that insulin downregulates GLUT4 both by depletion of GLUT4 in the GLUT4 storage compartment (GSC) and by accelerating degradation of the transporter in the lysosomes, which is induced by the H2O2 production by insulin. In the present study, we investigated the mechanism of insulin-stimulated production of H2O2 from two aspects: regulation of Nox4 activity and regulation of NADPH production. We found that Nox4, which is localized in the ER, binds to caveolae through post-translational modification by insulin and binds to the plasma membrane, and that insulin enhances NADPH production. The relevance of these two mechanisms needs to be further investigated.
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| Academic Significance and Societal Importance of the Research Achievements |
インスリンによるH2O2産生亢進メカニズムを明らかにすることは，脂肪細胞および骨格筋におけるインスリン抵抗性の発現メカニズム，を始めとする様々な生活習慣病の病態を解明する上で非常に重要であると考えられる。また細胞生物学およびシグナル伝達機構の領域においても，新たなインスリンシグナルによる細胞機能の調節機構を提示する可能性がある。
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