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the molecular mechanism of ER stress response in pancreatic beta cells : type 2 diabets

Research Project

Project/Area Number 22790842
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Metabolomics
Research InstitutionNihon University (2011)
Tohoku University (2010)

Principal Investigator

YAMAGUCHI Suguru  日本大学, 医学部, 助教 (70451614)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords膵β細胞 / 小胞体ストレス / 4E-BP1 / ATF6α / DPP-4阻害薬 / 糖尿病
Research Abstract

In the current study, we investigated 4E-BP1 expression, which is important for beta-cell survival, in MIN6 cells under ER stress and oxidative stress. We found that JNK activated by oxidative stress is involved in the modulation of 4E-BP1 expression and phosphorylation in MIN6 cells.
In this study, we analyzed Atf6α-null mice. ATF6α protects β-cells from ER stress and suppresses hepatosteatosis, but plays a role in the development of hyperlipidemia and insulin resistance.
The study is designed to investigate whether the activation of the incretin system by DPP-4 inhibition ameliorates β-cell failure in WFS1-deficient mice, a genetically defined model of human diabetes caused by ER stress in β-cells. These findings provide evidence that activation of the incretin system by vildagliptin plays a protective role against β-cells with WFS1-deficiency.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (14 results)

All 2012 2011 2010 Other

All Journal Article (5 results) (of which Peer Reviewed: 4 results) Presentation (9 results)

  • [Journal Article] Atf6α-null mice are glucose intolerant due to pancreatic β-cell failure on a high-fat diet but partially resistant to diet-induced insulin resistance2012

    • Author(s)
      Masahiro Usui, Suguru Yamaguchi, Yasuhiro Tanji, Ryu Tominaga, Yasushi Ishigaki, Manabu Fukumoto, Hideki Katagiri, Kazutoshi Mori, Yoshitomo Oka, Hisamitsu Ishihara
    • Journal Title

      Metabolism

      Volume: (in press)

    • Related Report
      2011 Final Research Report
  • [Journal Article] Involvement of endoplasmic stress protein C/EBP homologous protein in arteriosclerosis acceleration with augmented biological stress responses2011

    • Author(s)
      Gao J, Ishigaki Y, Yamada T, Kondo K, Yamaguchi S, Imai J, Uno K, HasegawaY, Sawada S, Ishihara H, Oyadomari S, Mori M, Oka Y, Katagiri H
    • Journal Title

      Circulation

      Volume: 124 Issue: 7 Pages: 830

    • DOI

      10.1161/circulationaha.110.014050

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The JNK pathway modulates expression and phosphorylation of the translational suppressor 4E-BP1 in MIN6 pancreatic beta-cells under oxidative stress conditions2010

    • Author(s)
      Tominaga R, Yamaguchi S, Satake C, Usui M, Tanji Y, Kondo K, Katagiri H, Oka Y, Ishihara H
    • Journal Title

      Cell Biochem Funct

      Volume: 28 Issue: 5 Pages: 387-393

    • DOI

      10.1002/cbf.1667

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The JNK pathway modulates expression and phosphorylation of the translational suppressor 4E-BP1 in MIN6 pancreatic β-cells under oxidative stress conditions2010

    • Author(s)
      Ryu Tominaga, Suguru Yamaguchi, Chihiro Satake, Masahiro Usui, Yasuhiro Tanji, Keiichi Kondo, Hideki Katagiri, Yoshitomo Oka, Hisamitsu Ishihara
    • Journal Title

      cell biochemistry and function

      Volume: 28(5) Pages: 387-393

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Atf6α-null mice are glucose intolerant due to pancreatic β-cell failure on a high-fat diet but partially resistant to diet-induced insulin resistance

    • Author(s)
      Masahiro Usui, Suguru Yamaguchi Yasuhiro Tanji, Ryu Tominaga, Yasushi Ishigaki, Manabu Fukumoto, Hideki Katagiri, Kazutoshi Mori, Yoshitomo Oka, Hisamitsu Ishihara
    • Journal Title

      Metabolism

      Volume: (In press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] ATF6α欠損マウスを用いた、ATF6α欠損が耐糖能に与える影響についての検討2011

    • Author(s)
      薄井正寛、石原寿光、鈴木千登世、山口賢、、石垣泰、福本学、森和俊、岡芳知、片桐秀樹
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2011-05-20
    • Related Report
      2011 Final Research Report
  • [Presentation] WFS1遺伝子欠損マウスにおけるDPP-4阻害薬(vildagliptin)の膵β細胞保護効果の検討2011

    • Author(s)
      丹治泰裕、山口賢、薄井正寛、冨永竜、近藤敬一、、石垣泰、岡芳知、片桐秀樹、石原寿光
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2011-05-20
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] GLP-1 exerts a protective role in pancreatic β-cells with WFS1-deficiency2011

    • Author(s)
      Suguru Yamaguchi, Yasuhiro Tanji, Masahiro Usui, Ryu Tominaga, Keiichi Kondo, Yasushi Ishigaki, Hideki Katagiri, Yoshitomo Oka, Hisamitsu Ishihara
    • Organizer
      The 47th EASD Annual Meeting
    • Place of Presentation
      Lisbon, Portugal
    • Related Report
      2011 Final Research Report
  • [Presentation] GLP-1 exerts a protective role in pancreatic β-cells with WFS1-deficiency2011

    • Author(s)
      Suguru Yamaguchi, Yasuhiro Tanji, Masahiro Usui, Ryu Tominaga, Keiichi Kondo, Yasushi Ishigaki, Hideki Katagiri, Yoshitomo Oka, Hisamitsu Ishihara
    • Organizer
      the 47th EASD Annual Meeting
    • Place of Presentation
      Lisbon, Portugal
    • Related Report
      2011 Annual Research Report
  • [Presentation] WFS1遺伝子欠損マウスに発表演目おけるDPP-4阻害薬(ビルダグリプチン)の膵β細胞保護効果の検討2010

    • Author(s)
      丹治泰裕、山口賢、薄井正寛、冨永竜、近藤敬一、石垣泰、片桐秀樹、岡芳知、石原寿光
    • Organizer
      第22回分子糖尿病学シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2010-12-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] ATF6α欠損マウスを用いた、ATF6α欠損が耐糖能に与える影響についての検討2010

    • Author(s)
      薄井正寛、石原寿光、鈴木千登世、山口賢、石垣泰、福本学、森和俊、岡芳知、片桐秀樹
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2010-05-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] 動脈硬化発症・進展におけるWFS1の役割の検討2010

    • Author(s)
      高俊弘、片桐秀樹、石垣泰、石原寿光、山田哲也、今井淳太、澤田正二郎、宇野健司、長谷川豊、山口賢、金子慶三、鈴木俊伸、齋藤徳郎、突田壮平、近藤敬一、高橋圭、檜尾好徳、岡芳知
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山
    • Related Report
      2011 Final Research Report
  • [Presentation] 膵β細胞における小胞体ストレス応答と酸化ストレス応答のクロストーク2010

    • Author(s)
      冨永竜、石原寿光、山口賢、佐竹千尋、薄井正寛、丹治泰裕、鈴木千登世、石垣泰、山田哲也、檜尾好徳、片桐秀樹、岡芳知
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 新規小胞体ストレス蛋白・CRELD2の蛋白特性についての検討2010

    • Author(s)
      山口賢、石原寿光、宗像佑一郎、佐竹千尋、薄井正寛、冨永竜、丹治泰裕、鈴木千登世、石垣泰、山田哲也、檜尾好徳、片桐秀樹、岡芳知
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山
    • Related Report
      2011 Final Research Report 2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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