New insights into diabetes onset in response to environmental factors through global transcriptome analysis of pancreatic islets isolated from a mouse model of type 2 diabetes

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461352
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: NAMMO Takao 国立研究開発法人国立国際医療研究センター, 代謝疾患研究部, 室長 (50594115)
• Co-Investigator(Renkei-kenkyūsha): YASUDA Kazuki 国立国際医療研究センター研究所, 代謝疾患研究部, 部長 (80311611)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: エネルギー・糖代謝異常 / 2型糖尿病 / 膵島 / 環境因子 / エピゲノム / 代償メカニズム / インスリン分泌 / 動物実験

Outline of Final Research Achievements

Although accumulating evidence supports a role for environmental factors in the development of diabetes, much remains unknown about the molecular mechanisms that are involved in the pathogenesis. Here, we report an analysis of transcriptome of mouse pancreatic islets isolated from a spontaneous mouse model of type 2 diabetes (T2D) exposed to a diabetogenic environment. We also generated genome-wide H3K27ac profiles to detect changes in cis-regulatory activity underlying differential gene expression. Compared to the control condition, we found that the environmental exposure resulted in lots of sites with decreased H3K27ac signals, which were associated to lower expression of corresponding genes. Interestingly, within such regions, there was enrichment of binding motifs for crucial transcription factors, suggesting that epigenetic dysregulation driven by environmental factors can cause downregulation of islet gene expression, beta-cell dysfunction, and the onset and progression of T2D.

Free Research Field

医歯薬学