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Analysis for new target gene of Mafa, and application for pancreatic beta-cell generation.

Research Project

Project/Area Number 24591328
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionOsaka University

Principal Investigator

MATSUOKA Takaaki  大阪大学, 医学(系)研究科(研究院), 講師 (10379258)

Co-Investigator(Kenkyū-buntansha) MIYATSUKA Takeshi  大阪大学, 医学系研究科, 特任講師 (60622363)
KANETO Hideaki  川崎医科大学, 医学部, 教授 (80448034)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords糖尿病 / インスリン合成 / インスリン転写因子 / 膵β細胞 / インスリン / Mafa / インスリン合成 / インスリン転写因子
Outline of Final Research Achievements

it is still unknown how Mafa is involved in insulin secrestion. To examine its mechanism, we performed ChIP assay with Mafa antibody and MIN6 cells followed by deep sequencing of isolated fragmented DNA. As a result, we could isolate several genes as target of Mafa. At least, one of them is clearly important for generating ATP and glucose-induced insulin secretion in pancreatic -cells. In another study, To explore the potential role of Mafa in reprogramming capacity in vivo, we generated transgenic mice conditionally expressing insulin transcription factors by the Cre/loxP system. Ectopic and combined expressions of those factors induced insulin producing cells from various non-beta-cells in vivo. Interestingly, the difference of original cell make different efficiency for the reprograming to insulin producing cells. These results demonstrated the critical role of Mafa for beta-cell function and generation.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (8 results)

All 2015 2014 2013 2012 Other

All Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (5 results)

  • [Journal Article] Preserving Mafa expression in diabetic islet β-cells improves glycemic control in vivo.2015

    • Author(s)
      Matsuoka TA, Kaneto H, Kawashima S, Miyatsuka T, Tochino Y, Yoshikawa A, Imagawa A, Miyazaki JI, Gannon M, Stein R, Shimomura I.
    • Journal Title

      J. Biol. Chem.

      Volume: 290 Issue: 12 Pages: 7647-57

    • DOI

      10.1074/jbc.m114.595579

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A novel function of Onecut 1 as a negative regulator of MafA.2013

    • Author(s)
      Yamamoto, K., Matsuoka T.
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Issue: 30 Pages: 21648-58

    • DOI

      10.1074/jbc.m113.481424

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 「糖尿病状態における膵β細胞機能障害の分子機構の解析」2012

    • Author(s)
      松岡孝昭
    • Journal Title

      糖尿病

      Volume: 第55巻 第12号 Pages: 948-951

    • NAID

      10031170436

    • Related Report
      2012 Research-status Report
  • [Presentation] 膵β細胞におけるMafa結合蛋白の重要性2014

    • Author(s)
      松岡孝昭
    • 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
      2014-05-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] インスリン転写因子Mafaの新規標的遺伝子同定の試み2014

    • Author(s)
      坂本扶美枝
    • 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
      2014-05-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] (リリー賞受賞講演)「糖尿病状態における膵β細胞機能障害の分子機構の解析」2012

    • Author(s)
      松岡孝昭
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 「Mafa結合蛋白の新規同定」2012

    • Author(s)
      松岡孝昭
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 膵β細胞へのdirect reprogramming 効率化に向けた試み

    • Author(s)
      松岡孝昭
    • Organizer
      日本糖尿病学会 年次総会
    • Place of Presentation
      熊本市
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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