| Project/Area Number |
18K06859
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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 48020:Physiology-related
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| Research Institution | Toho University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | カルシウムチャネル / β細胞 / インスリン / 脂質 / カルシウムシグナル / 分泌 |
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| Outline of Final Research Achievements |
Dysregulation of lipid metabolism leads to impaired insulin responsiveness and reduced insulin secretion. We have previously shown that the phospholipid transfer protein (Stard10) is involved in regulating lipid metabolism and interacts with voltage-gated L-type Ca2+ channels (CaV1.2). Recently, analysis of risk genes for type 2 diabetes reported that Stard10 may be involved in the regulation of insulin secretion in pancreatic beta cells. However, the mechanism by which lipid abnormalities reduce insulin secretion is unknown. Therefore, to elucidate the mechanism of reduced insulin secretion due to lipid abnormalities, we elucidated the mechanism linking Ca2+ signal regulation and lipid metabolism sensing/regulation and the involvement of lipid transfer protein.
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| Academic Significance and Societal Importance of the Research Achievements |
脂質異常によるインスリン分泌低下のメカニズム解明を目的として、Ca2+シグナル制御機構と脂質代謝のセンシング・調節の連携機構を、電位依存性L型Ca2+チャネル（CaV1.2）の分解機構と脂質転移蛋白の関与に注目して解析した。マウスβ細胞株（MIN6細胞）を用いてCaV1.2の発現、局在、細胞内Ca2+シグナル、インスリン分泌顆粒の動態をリアルタイム・イメージングにより解析し、脂質代謝の影響を解析した。その結果、脂肪酸依存的にCaV1.2の細胞膜発現量が制御されることを見出し、その制御を担う相互作用蛋白質候補を見出した。さらにインスリンを介したCaV1.2の細胞膜発現・局在の制御機構も見出した。
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