Abnormality of O-GlcNAcylation and pathogenesis of beta cell dysfunction

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09383
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Shiga University of Medical Science
• Principal Investigator: SEKINE OSAMU 滋賀医科大学, 医学部, 助教 (00402719)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: O-GlcNAc修飾 / 膵β細胞 / インスリン分泌 / 糖尿病

Outline of Final Research Achievements

O-GlcNAcylation is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (OGT) as the post-translational modification and serves in sensing intracellular nutrients by modulating various cellular process. Abnormality of O-GlcNAcylation may be associated with the pathogenesis of metabolic disease such as diabetes mellitus. We investigated insulin secretion and pancreatic beta cell function using tamoxifen-inducible pancreatic beta cell-specific Ogt-KO mice. These mice displayed transient hypoglycemia associated with higher insulin secretion and accelerated adiposity (early phase), followed by subsequent hyperglycemia with insulin depletion accompanied by beta cell apoptosis (late phase). In addition, tamoxifen-inducible global Ogt-KO mice exhibited a lethal phenotype from 4 weesks post injection. These findings suggest that O-GlcNAcylation plays a crucial role in pancreatic beta cell function and survival under physiological conditions.

Free Research Field

代謝学