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Analysis of molecular mechanisms underlying induction of insulin resistance in skeletal muscle

Research Project

Project/Area Number 25460365
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionKobe University

Principal Investigator

IJUIN TAKESHI  神戸大学, 医学(系)研究科(研究院), 助教 (00361626)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsSKIP / 骨格筋 / インスリンシグナル / インスリン抵抗性 / 小胞体ストレス / GRP78 / 2型糖尿病 / 筋小胞体 / PIP3 / 糖尿病 / インスリン / 小胞体
Outline of Final Research Achievements

Insulin resistance is characterized as a pathogenic factor in Type 2 diabetes. Here we show that skeletal muscle and kidney-enriched inositol polyphosphate phosphatase (SKIP), a phosphatidylinositol-3,4,5-trisphosphate (PIP3) phosphatase, and glucose-regulated protein 78 (GRP78) are implicated in inhibition of insulin-dependent PI 3-kinase signaling in skeletal muscle. We also show that SKIP links ER stress to insulin resistance in skeletal muscle. SKIP expression was increased due to ER stress, and was higher in the skeletal muscle isolated from high fat diet-fed mice and db/db mice than that from wild-type mice. Mechanistically, ER stress promotes activating transcription factor 6 (ATF6) and X-box binding protein 1 (XBP1)-dependent expression of SKIP. These findings underscore the specific and prominent role of SKIP in the development of insulin resistance in skeletal muscle.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (15 results)

All 2016 2015 2014 2013

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (9 results)

  • [Journal Article] Negatively-charged residues in the polar carboxy-terminal region in FSP27 are indispensable for expanding lipid droplets.2016

    • Author(s)
      Tamori Y, Tateya S, Ijuin T, Nishimoto Y, Nakajima S, Ogawa W.
    • Journal Title

      FEBS Lett.

      Volume: 590 Pages: 750-759

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of insulin signaling in skeletal muscle by PIP3 phosphatase, SKIP, and endoplasmic reticulum molecular chaperone glucose-regulated protein 78.2015

    • Author(s)
      Ijuin T, Hatano N, Hosooka T, Takenawa T.
    • Journal Title

      Biochimica et Biophysica Acta

      Volume: 1853(12) Issue: 12 Pages: 3192-3201

    • DOI

      10.1016/j.bbamcr.2015.09.009

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IRBIT Interacts with the Catalytic Core of Phosphatidylinositol Phosphate Kinase Type Iα and IIα through Conserved Catalytic Aspartate Residues. PLoS One. 10 e0141569 (2015).2015

    • Author(s)
      Ando H, Hirose M, Gainche L, Kawaai K, Bonneau B, Ijuin T, Itoh T, Takenawa T, Mikoshiba K.
    • Journal Title

      PLoS One

      Volume: 10 Issue: 10 Pages: 1-20

    • DOI

      10.1371/journal.pone.0141569

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phosphatidylinositol 3,4,5-Trisphosphate Phosphatase SKIP Links Endoplasmic Reticulum Stress in Skeletal Muscle to Insulin Resistance.2015

    • Author(s)
      Ijuin T, Hosooka T, Takenawa T.
    • Journal Title

      Mol Cell Biol.

      Volume: 36 Issue: 1 Pages: 108-118

    • DOI

      10.1128/mcb.00921-15

    • NAID

      120005819329

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Involvement of insulin signalingin myoblast cells by an addition of SKIP-binding peptide within Pak1 kinase domain.2015

    • Author(s)
      Ijuin, T. and Takenawa T.
    • Journal Title

      Biochem. Biophy. Res. Commun.

      Volume: 456 Issue: 1 Pages: 41-46

    • DOI

      10.1016/j.bbrc.2014.11.031

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Phosphatidylinositol 4-phosphate in the Golgi apparatus regulates cell-cell adhesion and invasive cell migration in human breast cancer.2014

    • Author(s)
      Tokuda, E., Itoh, T., Hasegawa, J., Ijuin, T., Takeuchi, Y., Irino, Y., Fukumoto, M., Takenawa, T.
    • Journal Title

      Cancer Res.

      Volume: 74 Issue: 11 Pages: 3054-3066

    • DOI

      10.1158/0008-5472.can-13-2441

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ホスホイノシチドホスファターゼSKIPは骨格筋でのインスリン抵抗性を惹起する2016

    • Author(s)
      伊集院 壮、竹縄 忠臣
    • Organizer
      第7回日本プロテインホスファターゼ研究会 学術集会
    • Place of Presentation
      岡崎
    • Year and Date
      2016-01-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] PAK1キナーゼドメイン中のPIP3ホスファターゼSKIP結合領域ペプチドを用いたイ ンスリン感受性改善への試み2015

    • Author(s)
      伊集院 壮、竹縄 忠臣
    • Organizer
      BMB2015
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞表面に存在する分子シャペロンGRP78によるPI3キナーゼシグナル制御機構2015

    • Author(s)
      伊集院 壮、竹縄 忠臣
    • Organizer
      第67回日本細胞生物学会
    • Place of Presentation
      東京
    • Year and Date
      2015-06-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] ホスホイノシチドホスファターゼSKIPによる新しい PI(4)P産生経路の解明2015

    • Author(s)
      伊集院 壮、竹縄 忠臣
    • Organizer
      第57回日本脂質生化学会
    • Place of Presentation
      東京
    • Year and Date
      2015-05-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] Pak1 acts as a scaffold function of protein phosphatases and phosphoinositide phosphatase in the negative regulation of growth factor signaling.2014

    • Author(s)
      伊集院壮、竹縄忠臣
    • Organizer
      第11回国際プロテインホスファターゼシンポジウム
    • Place of Presentation
      仙台
    • Year and Date
      2014-11-11 – 2014-11-14
    • Related Report
      2014 Research-status Report
  • [Presentation] ホスホイノシチドホスファターゼによる骨格筋におけるインスリンシ グナルの空間的な制御機構2014

    • Author(s)
      伊集院壮、竹縄忠臣
    • Organizer
      第56回日本脂質生化学会
    • Place of Presentation
      東大阪
    • Year and Date
      2014-06-06 – 2014-06-07
    • Related Report
      2014 Research-status Report
  • [Presentation] PIP3ホスファターゼSKIPによるPak1を介したPIP3の効率的な脱リン酸化機構2013

    • Author(s)
      伊集院 壮、竹縄 忠臣
    • Organizer
      第55回 日本脂質生化学会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] Pak1のscaffold機能を介したPI3キナーゼシグナルの終結機構2013

    • Author(s)
      伊集院 壮、竹縄 忠臣
    • Organizer
      第65回 日本細胞生物学会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report
  • [Presentation] 骨格筋におけるインスリンシグナル停止機構の時空間制御2013

    • Author(s)
      伊集院 壮、竹縄 忠臣
    • Organizer
      第86回 日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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