| Project/Area Number |
24591352
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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) |
IMACHI Hitomi 香川大学, 医学部, 准教授 (80380187)
TOKUMITSU Hiroshi 岡山大学, 自然科学研究, 教授 (20237077)
OHMORI Koji 香川大学, 医学部, 准教授 (00263913)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 糖尿病 / 代謝学 / HDL代謝 / 膵β細胞 / 脂肪毒性 / 糖毒性 / 細胞内情報伝達系 / インスリン分泌 / ABCA1 / GLP-1 / CaMKIV |
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| Outline of Final Research Achievements |
The reasons for beta-cell dysfunction in type 2 diabetes are incompletely understood. 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. A recent study reported that mice with specific inactivation of the Abca1 gene in their beta cells had markedly impaired glucose tolerance and defective insulin secretion, but normal insulin sensitivity. 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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