The elucidation of roles of GSK3 on the regulation of energy metabolism for developing therapeutic strategy of T2DM
| Project/Area Number |
25461357
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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 | Yamaguchi University |
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Principal Investigator |
TANABE Katsuya 山口大学, 医学部附属病院, 助教 (00397994)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 糖尿病 / GSK3 / 膵β細胞 / 小胞体ストレス / エネルギー代謝 / PPARγ / GSK-3 / 脂肪細胞 / アポトーシス |
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| Outline of Final Research Achievements |
We aimed to elucidate the pathophysiological roles of GSK-3 in developing type 2 diabetes. Inactivation of the GSK3 attenuated ER stress-induced β-cell apoptosis with concomitant inhibition ATF4 protein degradation. As a consequence of ATF4 modulation, GSK-3 inhibition resulted in an alteration of translational adaptation to ER stress. On the other hand, GSK3 is activated in adipose tissue of mice fed high fat diet. In addition, GSK-3 negatively regulates transcriptional activity of PPARγ by giving a direct phosphorylation, suggesting that it may play an important role in the regulation of energy metabolism. These results indicate that aberrant activation of GSK3 is implicated to both β-cell loss and a modulation of energy metabolism. Therefore, understanding the mechanisms by which GSK3 modulates glucose metabolism helps developing new strategy to the treatment of type 2 diabetes.
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features.2014
Author(s)
Matsunaga K, Tanabe K, Inoue H, Okuya S, Ohta Y, Akiyama M, Taguchi A, Kora Y, Okayama N, Yamada Y, Wada Y, Amemiya S, Sugihara S, Nakao Y, Oka Y, Tanizawa Y.
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Journal Title
PLOS ONE
Volume: 9
Issue: 9
Pages: e106906-e106906
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] A sibling case of Wolfram syndrome with a novel mutation Y652X in WFS12013
Author(s)
Iwasaki N., Fukawa K., Matsuo M., Urano M., Watanabe M., Ono Y., Tanabe K., Tanizawa Y., Ogata M., Ide R., Takizawa M., Nagata S., Osawa M., Uchigata Y., Saito K.
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Journal Title
Diabetology International
Volume: 5
Issue: 2
Pages: 148-153
DOI
Related Report
Peer Reviewed
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