| Project/Area Number |
15K09415
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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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| Research Field |
Metabolomics
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| Research Institution | Kagawa University |
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Principal Investigator |
MURAO Koji 香川大学, 医学部, 教授 (20291982)
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| Co-Investigator(Kenkyū-buntansha) |
大森 浩二 香川大学, 医学部, 准教授 (00263913)
井町 仁美 香川大学, 医学部, 准教授 (80380187)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 糖尿病 / 代謝学 / HDL代謝 / 膵β細胞 / 脂肪毒性 / トランスレーショナルリサーチ / 細胞内情報伝達系 / インスリン分泌 / ABCA1 / HDL / 膵β脂肪 / 転写調節 / 転写因子PREB / PREB / Akt / PI3K / insulin / IGF-I |
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| Outline of Final Research Achievements |
Recently, abnormalities in cholesterol metabolism have emerged as a potential contributor to beta-cell dysfunction. ATP-binding cassette transporter A1 (ABCA1), a cytoplasmic membrane protein, is a pivotal regulator of lipid efflux from cells to apolipoproteins and plays an important role in reverse cholesterol transport. Pancreatic islets isolated from ABCA1-deficient mice demonstrated altered cholesterol homeostasis and impaired insulin secretion in vitro. We have revealed the link between ABCA1 signal transduction pathway and transcriptional factor that regulated ABCA1 gene expression. Pancreatic islets isolated from these mice demonstrated altered cholesterol homeostasis and impaired insulin secretion in vitro. These results establish a new role for the ABCA1 gene in beta cell cholesterol homeostasis and insulin secretion, indicating that cholesterol accumulation may contribute to beta cell dysfunction in type 2 diabetes, so called “pancreatic lipotoxicity”.
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