Long-Term Pancreatic Beta Cell Exposure To High Levels of Glucose but not Palmitate induces DNA Methylation within the Insulin Gene Promoter and represses Transcriptional Activity

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790920
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Nagoya University
• Principal Investigator: TSUNEKAWA Shin 名古屋大学, 医学部附属病院, 助教 (40612768)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: エピジェネティクス

Outline of Final Research Achievements

Genetic and environmental factors influence the development of type 2 diabetes, and especially nutritional condition is a major component of environmental factor. Recently, DNA methylation of Insulin gene promoter has been reported to suppress insulin gene expression and be elevated in the subject with diabetes.
Our study demonstrated that under over-nutritional condition, glucotoxicity, but not lipotoxicity, was essential for DNA methylation of Insulin gene promoter as well as insulin expression in pancreatic beta cell. Glucotoxicity increased the DNA methylation in time- and glucose concentration- dependent manner. Glucotoxicity increased DNA methyltransferase activity and decreased ten-eleven-translocation hydroxylase activity. Ectopic triglyceride accumulation was increased parallel to DNA methylation by glucotoxicity in pancreatic beta cells. This study helps to clarify the effect of an over-nutrition state on DNA methylation of the Ins1 promoter in pancreatic beta cells.

Free Research Field

糖尿病学