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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

Research Project

Project/Area Number 26461352
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionNational 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
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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 / エネルギー・糖質代謝異常
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.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (12 results)

All 2017 2016 2015 2014 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (5 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Genome-wide DNA methylation analysis during non-alcoholic steatohepatitis-related multistage hepatocarcinogenesis: comparison with hepatitis virus-related carcinogenesis.2017

    • Author(s)
      Kuramoto J, Arai E, Tian Y, Funahashi N, Hiramoto M, Nammo T, Nozaki Y, Takahashi Y, Ito N, Shibuya A, Ojima H, Sukeda A, Seki Y, Kasama K, Yasuda K, Kanai Y.
    • Journal Title

      Carcinogenesis.

      Volume: 38 Issue: 3 Pages: 261-270

    • DOI

      10.1093/carcin/bgx005

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Characterization of hepatic lipid profiles in a mouse model with nonalcoholic steatohepatitis and subsequent fibrosis2015

    • Author(s)
      Saito K, Uebanso T, Maekawa K, Ishikawa M, Taguchi R, Nammo T, Nishimaki-Mogami T, Udagawa H, Fujii M, Shibazaki Y, Yoneyama H, Yasuda K, Saito Y.
    • Journal Title

      Sci Rep.

      Volume: 5 Issue: 1 Pages: 12466-12466

    • DOI

      10.1038/srep12466

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Comparative analysis of type 2 diabetes-associated SNP alleles identifies allele-specific DNA-binding proteins for the KCNQ1 locus.2015

    • Author(s)
      Hiramoto M, Udagawa H, Watanabe A, Miyazawa K, Ishibashi N, Kawaguchi M, Uebanso T, Nishimura W, Nammo T, Yasuda K.
    • Journal Title

      Int J Mol Med.

      Volume: 36 Issue: 1 Pages: 222-2230

    • DOI

      10.3892/ijmm.2015.2203

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Druggable oncogene fusions in invasive mucinous lung adenocarcinoma.2014

    • Author(s)
      Nakaoku T, Tsuta K, Ichikawa H, Shiraishi K, Sakamoto H, Enari M, Furuta K, Shimada Y, Ogiwara H, Watanabe S, Nokihara H, Yasuda K, Hiramoto M, Nammo T, Ishigame T, Schetter AJ, Okayama H, Harris CC, Kim YH, Mishima M, Yokota J, Yoshida T, Kohno T
    • Journal Title

      Clin Cancer Res

      Volume: 20 Issue: 12 Pages: 3087-3093

    • DOI

      10.1158/1078-0432.ccr-14-0107

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Comprehensive exploration of novel chimeric transcripts in clear cell renal cell carcinomas using whole transcriptome analysis.2014

    • Author(s)
      Gotoh M, Ichikawa H, Arai E, Chiku S, Sakamoto H, Fujimoto H, Hiramoto M, Nammo T, Yasuda K, Yoshida T, Kanai Y.
    • Journal Title

      Genes Chromosomes Cancer

      Volume: 53 Issue: 12 Pages: 1018-1032

    • DOI

      10.1002/gcc.22211

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ゲノム網羅的解析結果を用いた膵島代償機序の検討2016

    • Author(s)
      南茂隆生、宇田川陽秀、舟橋伸昭、川口美穂、上番増喬、平本正樹、西村渉、安田和基
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      京都
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 遺伝子cis調節領域の網羅的解析による膵島代償機序の検討2016

    • Author(s)
      南茂隆生、宇田川陽秀、舟橋伸昭、川口美穂、上番増喬、平本正樹、西村渉、安田和基
    • Organizer
      第53回日本臨床分子医学会
    • Place of Presentation
      東京
    • Year and Date
      2016-04-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] 網羅的cis調節領域の検討による、高脂肪食に続発する膵島代償機序の解明2015

    • Author(s)
      南茂 隆生、宇田川 陽秀、舟橋 伸昭、安田 和基
    • Organizer
      NGS現場の会 第四回研究会
    • Place of Presentation
      茨城
    • Year and Date
      2015-07-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 膵島のゲノム網羅的解析による膵島代償機序/糖尿病発症機序関連因子の同定2015

    • Author(s)
      南茂 隆生、宇田川 陽秀、川口 美穂、舟橋 伸昭、上番増 喬、平本 正樹、西村 渉、安田 和基
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      山口
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 膵島のゲノム網羅的解析による糖尿病発症機序の考察2014

    • Author(s)
      南茂隆生、宇田川陽秀、川口美穂、舟橋伸昭、上番増喬、平本正樹、西村渉、安田和基
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-24
    • Related Report
      2014 Research-status Report
  • [Book] 膵β細胞分化過程におけるエピゲノム変化、内分泌・糖尿病・代謝内科2014

    • Author(s)
      南茂 隆生、安田 和基
    • Total Pages
      8
    • Publisher
      科学評論社
    • Related Report
      2014 Research-status Report
  • [Remarks] 代謝疾患研究部

    • URL

      http://www.rincgm.jp/department/dia/02/

    • Related Report
      2016 Annual Research Report 2015 Research-status Report 2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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