DOC2b regulates GLUT4 vesicle fusion mediated aPKC activation.

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461356
• 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: FUKUDA Naofumi 山口大学, 医学部附属病院, 助教 (50566867)
• Co-Investigator(Kenkyū-buntansha): TANIZAWA Yukio 山口大学, 大学院医学系研究科, 教授 (00217142)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Glut4 / DOC2b / atypical PKC

Outline of Final Research Achievements

DOC2b is a member of Synaptotagmin family proteins that have tandem C2 domains. We previously found that DOC2b translocated to the plasma membrane and bound syntaxin-4 on insulin stimulation , mediating GLUT4 vesicle fusion. In this study, we investigated the role of DOC2b on systemic glucose homeostasis.
DOC2b-/- mice showed insulin resistance and impaired glucose tolerance. Insulin-stimulated glucose uptake was impaired in isolated soleus muscle of the DOC2b-/- mice. We also investigated signaling molecule mediating insulin signal to DOC2b. By immunoprecipitation, we identified an isoform of atypical PKC (aPKC) binding to DOC2b. When kinase dead aPKC or mutant DOC2b was overexpressed in the 3T3-L1 adopocytes, DOC2b did not translocate to the plasma on insulin stimulation. GLUT4 vesicle fusion regulated by DOC2b is important for the systemic glucose homeostasis. An isoform of aPKC is likely to regulate DOC2b translocation and GLUT4 vesicle fusion in response to insulin.

Free Research Field

糖尿病