| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| 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.
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