Relationship between islet b-cell failure and phosphorylation of b-cell specific transcription factor MafA

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461353
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Yokohama City University
• Principal Investigator: Kataoka Kohsuke 横浜市立大学, 生命医科学研究科, 准教授 (20262074)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 糖尿病 / 細胞内シグナル伝達 / 遺伝子発現制御

Outline of Final Research Achievements

During progression of type-2 diabetes, pancreatic islet b-cells gradually lose their ability to produce and secrete Insulin in response to high blood glucose. To clarify molecular mechanism of the b-cell failure, I analyzed function and activity of b-cell specific transcription factor MafA in b-cells during diabetes progression.
I found that multiple phosphorylation events on MafA regulates its interaction with Beta2, another important transcriptional regulator of b-cell function. I also found that multiple protein kinases phosphorylate MafA redundantly. In b-cells of type-2 diabetes model mice db/db, intracellular distribution and/or abundance of these kinases change during progression of diabetes. Elucidating the mechanism of regulation of these kinases in b-cells may lead to understanding of b-cell failure and contribute to prevention and treatment of diabetes .

Free Research Field

内分泌学