Mechanism of insulin regulation of spatial and temporal fate of GLUT4

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08463
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Gunma University
• Principal Investigator: Shibata Hiroshi 群馬大学, 生体調節研究所, 准教授 (20235584)
• Project Period (FY): 2018-04-01 – 2021-03-31
• 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

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.

Free Research Field

細胞生物学

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。