Establishing a base for tailor-made therapy on diabetes from the view point of the pancreatic beta cell mass

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390235
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Yokohama City University
• Principal Investigator: TERAUCHI Yasuo 横浜市立大学, 医学(系)研究科(研究院), 教授 (40359609)
• Co-Investigator(Kenkyū-buntansha): SHIRAKAWA Jun 横浜市立大学, 医学(系)研究科(研究院), 客員研究員 (70625532)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 膵β細胞 / グルコキナーゼ / グルコースシグナル

Outline of Final Research Achievements

We investigated changes in the expression of genes involved in beta cell function and proliferation in mouse islets stimulated with glucokinase activator (GKA) in order to elucidate the mechanisms by which GKA stimulates beta cell function and proliferation. GKA-stimulated IRS2 production affected beta cell proliferation but not beta cell function. We investigated the impact of glucokinase activation by GKA on ER stress in β cells. GKA administration improved β-cell apoptosis in Akita mice, a model of ER stress-mediated diabetes. GKA ameliorated ER stress-mediated apoptosis by harmonizing IRS-2 upregulation and the IRS-2-independent control of apoptosis in β cells. IRS-2 knockout mice exhibited an enhancement in β-cell proliferation after a pancreatectomy equal to that observed in wild-type mice. A pancreatectomy stimulated β-cell proliferation via a signaling pathway different from that involved in high-fat diet-induced β-cell expansion.

Free Research Field

糖尿病学