| 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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| 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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