The pathophysiological role of pancreatic beta-cell hypoxia in the progression of diabetes
| 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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Report
(3 results)
Research Products
(15 results)
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[Journal Article] SIRT7 controls hepatic lipid metabolism by regulating the ubiquitin-proteasome pathway.2014
Author(s)
Yoshizawa T, Karim Md. F, Sato Y, Senokuchi T, Miyata K, Fukuda T, Go C, Tasaki M, Uchimura K, Kadomatsu T, Tian Z, Smolka C, Sawa T, Kakeya M, Tomizawa K, Ando Y, Araki E, Akaike T, Braun T, Oike Y, Bober E, Yamagata K.
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Journal Title
Cell Metab.
Volume: 9
Issue: 4
Pages: 712-721
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Interferon stimulated gene 15 has an anti-apoptotic effect on MIN6 cells2014
Author(s)
Yoshikawa A, Imagawa A, Nakata S, Fukui K, Kuroda Y, Miyata Y, Sato Y, Hanafusa T, Matsuoka TA, Kaneto H, Iwahashi H, Shimomura I.
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Journal Title
Endocrine Journal
Volume: 61
Issue: 9
Pages: 883-890
DOI
NAID
ISSN
0918-8959, 1348-4540
Related Report
Peer Reviewed / Acknowledgement Compliant
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