| Project/Area Number |
23791044
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Metabolomics
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
FUJIMOTO Kei 東京慈恵会医科大学, 医学部, 講師 (40372974)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | エネルギー / 糖質代謝異常 / 膵β細胞容積 / β細胞死 / アポトーシス / MODY / β細胞容積 |
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| Research Abstract |
Glucose and fatty acid contribute to beta cell death destruction in diabetes, but the mechanisms are incompletely understood. The aim of the current study was to address the role of the protein kinase C (PKC) isoform PKCdelta, a diverse regulator of cell death, in glucose and fatty acid-induced cell death in beta cells. Mouse insulinoma cell line MIN6 cells were treated with glucose and free fatty acid (palmitate) and assayed for MIN6 cell death by propidium iodide (PI)-staining and TUNEL assays. Signaling pathways were determined by immunoblotting and promoter assays. PKCdelta overexpression in MIN6 cells induced cell death as assessed by PI-staining and TUNEL assays accompanied with increased cleaved caspase-3 by immunoblotting. Interestingly, PKCdelta induced Nix promoter activity and Nix protein expression. Deficiency of PKCdelta inhibited MIN6 cell death with glucose and palmitate (Glucolipotoxicity model). PKCdelta deficiency partially protects against glucose and fatty acid in beta cells. This might be partly dependent by cell death molecule Nix. These results highlight a mechanism for regulating beta cell death in glucolipotoxicity condition such as in obese type 2 diabetes.
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