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Effect of cPLA_2 inhibition on improvement of glucose tolerance through PPARγ activation

Research Project

Project/Area Number 19591056
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionKumamoto University

Principal Investigator

MATSUMURA Takeshi  Kumamoto University, 医学部・附属病院, 医員 (20398192)

Co-Investigator(Kenkyū-buntansha) MIYAMURA Nobuhiro  熊本大学, 医学部・附属病院, 講師 (40274716)
MOTOSHIMA Hiroyuki  熊本大学, 医学部・附属病院, 医員 (40398201)
西川 武志  熊本大学, 大学院・医学薬学研究部, 助教 (70336212)
Co-Investigator(Renkei-kenkyūsha) NISHIKAWA Takeshi  熊本大学, 医学部・附属病院, 助教 (70336212)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordscPLA_2 / 脂肪細胞 / マクロファージ / インスリン抵抗性 / 糖尿病 / PPARγ / COX-2 / 動脈硬化 / cPLA2
Research Abstract

本研究は、cytosolic phospholipase A_2(cPLA_2)の制御によるPPARγ活性化の機序を解明し、その効果を介したインスリン抵抗性改善作用の有無を探求することを目的とし検討を行った。その結果、cPLA_2の阻害がマクロファージあるいは脂肪細胞においてCOX-2産生増加を介してPPARγの活性化を誘導すること、脂肪細胞分化誘導を促進すること、さらに高脂肪食負荷マウスの耐糖能を改善することを見出した。これらの成果は、cPLA_2が2型糖尿病治療の標的分子であると共に、cPLA_2阻害剤が糖尿病治療に有益である可能性を示唆している。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (20 results)

All 2009 2008 2007

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (6 results)

  • [Journal Article] TZDs reduce mitochondrial ROS production and enhance mitochondrial biogenesis.2009

    • Author(s)
      Fujisawa K
    • Journal Title

      Biochem Biophys Res Commun. 379

      Pages: 43-48

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and protects against atherosclerosis.2009

    • Author(s)
      Adachi H
    • Journal Title

      Biochem Biophys Res Commun. 379

      Pages: 806-811

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ox-LDL activates PPARα and PPARγ through MAPK-dependent COX-2 expression in macrophages2008

    • Author(s)
      Taketa K, Matsumura T, Yano M, Ishii N, Senokuchi T, Motoshima H, Murata Y, Kim-Mitsuyama S, Kawada T, Itabe H, Takeya M, Nishikawa T, Tsuruzoe K, Araki E
    • Journal Title

      J Biol Chem 283

      Pages: 9852-9862

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic mice2008

    • Author(s)
      Goto H, Nishikawa T, Sonoda K, Kondo T, Kukidome D, Fujisawa K, Yamashiro T, Motoshima H, Matsumura T, Tsuruzoe K, Araki E
    • Journal Title

      Biochem Biophys Res Commun 366

      Pages: 814-820

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rottlerin activates AMPK possibly through LKB1 in vascular cells and tissues2008

    • Author(s)
      Kojima K, Motoshima H, Tsutsumi A, Igata M, Matsumura T, Kondo T, Kawashima J, Ichinose K, Furukawa N, Inukai K, Katayama S, Goldstein BJ, Nishikawa T, Tsuruzoe K, Araki E
    • Journal Title

      Biochem Biophys Res Commun 376

      Pages: 434-438

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rottlerin activates AMPK possibly through LKBI in vascular cells and tissues.2008

    • Author(s)
      Kojima K
    • Journal Title

      Biochem Biophys Res Commun. 376

      Pages: 434-438

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ox-LDL activates PPARα and PPARγ through MAPK-dependent COX-2 expression in macronhases.2008

    • Author(s)
      Taketa K.
    • Journal Title

      Journal of Biological Chemistry 283

      Pages: 9852-9862

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Statins activate peroxisome proliferator-activated receptor-γ through extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase-dependent cyclooxygenase-2 expression in macrophages2007

    • Author(s)
      Yano M, Matsumura T, Senokuchi T, Ishii N, Murata Y, Taketa K, Motoshima H, Taguchi T, Sonoda K, Kukidome D, Takuwa Y, Kawada T, Brownlee M, Nishikawa T, Araki E
    • Journal Title

      Circ Res 100

      Pages: 1442-1451

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Troglitazone inhibits oxidized low-density lipoprotein-induced macrophage proliferation : impact of the suppression of nuclear translocation of ERK1/22007

    • Author(s)
      Yano M, Matsumura T, Senokuchi T, Ishii N, Motoshima H, Taguchi T, Matsuo T, Sonoda K, Kukidome D, Sakai M, Kawada T, Nishikawa N, Araki E
    • Journal Title

      Atherosclerosis 191

      Pages: 22-32

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] High glucose increases angiopoietin-2 transcription in microvascular endothelial cellsthrough methylglyoxal modification of mSin3A2007

    • Author(s)
      Yao D, Taguchi T, Matsumura T, Pestell R, Edelstein D, Giardino I, Suske G, Rabbani N, Thornalley PJ, Sarthy VP, Hammes HP, Brownlee M
    • Journal Title

      J Biol Chem 282

      Pages: 31038-31045

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impact of mitochondrial ROS production in the pathogenesis of insulin resistance2007

    • Author(s)
      Nishikawa T, Kukidome D, Sonoda K, Fujisawa K, Matsuhisa T, Motoshima H, Matsumura T, Araki E
    • Journal Title

      Diabetes Res Clin Pract 77Suppl1

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impact of mitochondrial ROS production on diabetic vascular complications2007

    • Author(s)
      Nishikawa T, Kukidome D, Sonoda K, Fujisawa K, Matsuhisa T, Motoshima H, Matsumura T, Araki E
    • Journal Title

      Diabetes Res Clin Pract 77Suppl1

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A.2007

    • Author(s)
      Yao D
    • Journal Title

      Journal of Biological Chemistry 282

      Pages: 31038-31045

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Statins activate Peroxisome Proliferator-Activated Receptor γ through extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase-dependent cyclooxygenase-2 expression in macrophages.2007

    • Author(s)
      Yano M
    • Journal Title

      Circulation Research 100

      Pages: 1442-1451

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] スタテン製剤によるPPARγ活性化を介した多面的効果の検討2008

    • Author(s)
      松村 剛
    • Organizer
      第58回日本体質医学会総会
    • Place of Presentation
      メルパルク京都(京都市)
    • Year and Date
      2008-09-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] ニフェジピンによるPPARγ活性化を介した抗動脈硬化作用機序の解明2008

    • Author(s)
      松村剛, 石井規夫, 木下博之, 中尾紗綾, 本島寛之, 西川武志, 荒木栄一
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札幌
    • Related Report
      2008 Final Research Report
  • [Presentation] スタチン製剤による抗動脈硬化作用の新規機序解明-PPARα, PPARγ活性誘導効果の関与2007

    • Author(s)
      松村剛, 矢野美由紀, 石井規夫, 荒木栄一
    • Organizer
      第15回日本血管生物医学会学術大会
    • Place of Presentation
      福岡
    • Related Report
      2008 Final Research Report
  • [Presentation] スタチンによるPPARα, PPARγを介した抗動脈硬化作用の解明2007

    • Author(s)
      松村剛, 矢野美由紀, 石井則夫, 竹田佳代, 村田雄介, 瀬ノ口隆文, 本島寛之, 西川武志, 荒木栄一
    • Organizer
      第39回日本動脈硬化学会総会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] スタチン製剤による抗動脈硬化作用の新規機序解明-PPARα, PPARγ活性誘導効果の関与2007

    • Author(s)
      松村剛, 矢野美由紀, 石井則夫, 村田雄介, 竹田佳代, 瀬ノ口隆文, 本島寛之, 西川武志, 荒木栄一
    • Organizer
      第50回日本糖尿病学会総会
    • Place of Presentation
      仙台
    • Related Report
      2008 Final Research Report
  • [Presentation] Statins induce anti-atherosclerotic effect via activation of PPARα and PPARγ2007

    • Author(s)
      Matsumura T.
    • Organizer
      第39回日本動脈硬化学会総会
    • Place of Presentation
      大阪国際会議場
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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