| Project/Area Number |
26860697
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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 | Kumamoto University |
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Principal Investigator |
SATO Yoshifumi 熊本大学, 大学院生命科学研究部(医), 助教 (90622598)
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| Research Collaborator |
YAMAGATA Kazuya 熊本大学, 大学院生命科学研究部, 教授 (70324770)
INOUE Masahiro 大阪府立病院機構大阪府立成人病センター, 生化学部門, 部長 (10342990)
KONDOH Shinae 東京工業大学, 生命理工学研究科, 教授 (40314182)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 糖尿病 / 低酸素 / 膵β細胞 |
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| Outline of Final Research Achievements |
The islets (pancreatic beta-cells) of a diabetic mouse become hypoxic. However, how the beta cells become hypoxic under diabetic conditions and what kinds of molecules are related to the beta-cell dysfunction by hypoxia, which still remain unclear. In this study, we generated hypoxia-imaging mice to monitor islet hypoxia in diabetes by crossbreeding an oxygen dependent domain (ODD)-Luciferase transgenic (Tg) mouse with diabetes model mice (ob/ob or db/db mouse). Furthermore, we found that beta-cell hypoxia causes less ATP production by reduced mitochondrial complex Ⅰactivity and abnormal beta-cell gene expression patterns, which results in reduced insulin secretion. And Hypoxia-inducible factor(HIF)-1, a master regulator in hypoxia response didn't contribute to the dysregulated gene expression and impaired insulin secretion by hypoxia. From this aspect, further studies are needed to clarify a HIF-1-independent hypoxia response pathway in beta-cells.
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