Analysis of insulin resistance through DGKz and development of anti-diabetic medicine

2015 Fiscal Year Final Research Report

• Project/Area Number: 24380152
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Applied animal science
• Research Institution: The University of Tokyo
• Principal Investigator: Hakuno Fumihiko 東京大学, 農学生命科学研究科, 助教 (30282700)
• Co-Investigator(Kenkyū-buntansha): ITO Akihiro 独立行政法人理化学研究所, 吉田化学遺伝学研究室, 専任研究員 (40391859)
• Co-Investigator(Renkei-kenkyūsha): TAKAHASHI Shin-Ichiro 東京大学, 大学院農学生命科学研究科, 准教授 (00197146)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: インスリン / 糖尿病 / 糖輸送担体 / ジアシルグリセロールキナーゼ / インスリン抵抗性 / 低分子化合物

Outline of Final Research Achievements

We showed that DGKζ regulates insulin-induced GLUT4 translocation to PM in a canonical insulin-signal independent manner. In addition, DGKζ-associated protein, PIP5K1α modulates GLUT4 translocation in a similar mechanism as DGKζ.
By using ELISA kit, we succeeded to identify around 30 small compounds which inhibit the interaction between IRS-1 and DGKζ. Addition of one of these compounds, Compound A, inhibited the interaction between IRS-1 and DGKζ in HEK293T cells. Moreover Compound A addition recovered TNF-α-induced insulin resistance in 3T3-L1 adipocytes.

Free Research Field

分子内分泌制御学