The elucidation of roles of GSK3 on the regulation of energy metabolism for developing therapeutic strategy of T2DM

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461357
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Yamaguchi University
• Principal Investigator: TANABE Katsuya 山口大学, 医学部附属病院, 助教 (00397994)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 糖尿病 / GSK3 / 膵β細胞 / 小胞体ストレス / エネルギー代謝 / PPARγ

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.

Free Research Field

代謝学