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Regulation mechanisms of diacylglycerol kinase delta in differentiation and development of skeletal muscle to prevent exaggeration of type 2 diabetes

Research Project

Project/Area Number 20K07049
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionShimane University

Principal Investigator

Sakai Hiromichi  島根大学, 学術研究院医学・看護学系, 助教 (00375255)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords2型糖尿病 / ジアシルグリセロールキナーゼ / 骨格筋 / 筋形成 / ミリスチン酸 / 褐色脂肪組織 / 骨格筋形成 / β-tubulin / 筋再生 / 脂質代謝経路
Outline of Research at the Start

2型糖尿病の改善のためには,食生活の乱れや運動不足により低下した骨格筋の機能(インスリン感受性・グルコース取り込み能)と量の回復が重要である.骨格筋に高発現するジアシルグリセロールキナーゼδ(DGKδ)はインスリン感受性・グルコース取り込み能の維持・亢進に決定的な役割を担っているが,さらに,本研究により,①細胞レベルでDGKδによる筋分化制御機構の詳細を解明し,②個体レベルでDGKδの発現変動による筋形成への影響を明らかにすることで,骨格筋の機能改善と量増加の両方を目指した二重に効果的な,DGKδを分子標的とした新規2型糖尿病治療法の開発へと展開するための基礎的知見を提供する.

Outline of Final Research Achievements

Diacylglycerol kinase δ (DGKδ) positively regulates myogenic differentiation of C2C12 myoblasts, but the molecular mechanisms of its myogenesis and development into skeletal muscle are still unknown. In this study, we found that myristic acid, which upregulates DGKδ expression levels and glucose uptake in myotubes, increased DGKδ-dependently the expression levels of β-tubulin, one of important factors for muscle development, in C2C12 myotubes. Moreover, to investigate the development of skeletal muscle, we generated the skeletal muscle-specific DGKδ-knockout mice. The mice showed the approximately 10% reduction of body weight and skeletal muscle. In addition, brown adipocyte tissue was also decreased. In near future, we will reveal the roles of DGKδ on skeletal muscle and brown adipocyte tissue.

Academic Significance and Societal Importance of the Research Achievements

2型糖尿病(インスリン抵抗性)の改善のためには,食生活の乱れや運動不足により低下した骨格筋の機能(グルコース取り込み能)と量の回復が重要である.DGKδは骨格筋のグルコース取り込みに重要であり,一方で,DGKδが細胞レベルで筋分化誘導を正に制御する知見を得たが,筋形成における詳細な機構はわかっていなかった.今回,筋細胞のDGKδの発現を増加させるミリスチン酸がDGKδ発現依存的に筋形成に重要な役割を担うβ-tubulinの発現を増加させることを示した.この知見は,DGKδの発現増加は2型糖尿病患者で低下するグルコースの取り込み能と筋量の両方を改善する可能性を示している.

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (17 results)

All 2023 2022 2021 2020 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Analysis of the time-dependent changes of phospholipids in the brain regions of a mouse model of Alzheimer’s disease2023

    • Author(s)
      Ahsanul Haque Md.、Omori Naoki、Md. Sheikh Abdullah、Yano Shozo、Osago Harumi、Mitaki Shingo、Kalam Azad Abul、Sakai Hiromichi、Michikawa Makoto、Nagai Atsushi
    • Journal Title

      Brain Research

      Volume: 1800 Pages: 148197-148197

    • DOI

      10.1016/j.brainres.2022.148197

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Myristic acid selectively augments β‐tubulin levels in C2C12 myotubes via diacylglycerol kinase δ2022

    • Author(s)
      Sakai Hiromichi、Matsumoto Ken‐ichi、Urano Takeshi、Sakane Fumio
    • Journal Title

      FEBS Open Bio

      Volume: 12 Issue: 10 Pages: 1788-1796

    • DOI

      10.1002/2211-5463.13466

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Time-Dependent Analysis of Plasmalogens in the Hippocampus of an Alzheimer’s Disease Mouse Model: A Role of Ethanolamine Plasmalogen2021

    • Author(s)
      Azad Abul Kalam、Sheikh Abdullah Md.、Haque Md. Ahsanul、Osago Harumi、Sakai Hiromichi、Shibly Abu Zaffar、Yano Shozo、Michikawa Makoto、Hossain Shahdat、Tabassum Shatera、A. Garu、Zhou Xiaojing、Zhang Yuchi、Nagai Atsushi
    • Journal Title

      Brain Sciences

      Volume: 11 Issue: 12 Pages: 1603-1603

    • DOI

      10.3390/brainsci11121603

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rapid identification of plasmalogen molecular species using targeted multiplexed selected reaction monitoring mass spectrometry2021

    • Author(s)
      Azad Abul Kalam、Kobayashi Hironori、Md. Sheikh Abdullah、Osago Harumi、Sakai Hiromichi、Ahsanul Haque Md.、Yano Shozo、Nagai Atsushi
    • Journal Title

      Journal of Mass Spectrometry and Advances in the Clinical Lab

      Volume: 22 Pages: 26-33

    • DOI

      10.1016/j.jmsacl.2021.09.004

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Roles of Diacylglycerol Kinase α in Cancer Cell Proliferation and Apoptosis2021

    • Author(s)
      Sakane Fumio、Hoshino Fumi、Ebina Masayuki、Sakai Hiromichi、Takahashi Daisuke
    • Journal Title

      Cancers

      Volume: 13 Issue: 20 Pages: 5190-5190

    • DOI

      10.3390/cancers13205190

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diacylglycerol kinase eta regulates C2C12 myoblast proliferation through mTOR signaling pathway.2020

    • Author(s)
      Hiromichi Sakai, Chiaki Murakami, Qiang Lu, Ken-ichi Matsumoto, Takeshi Urano and Fumio Sakane.
    • Journal Title

      Biochimie

      Volume: 177 Pages: 13-24

    • DOI

      10.1016/j.biochi.2020.07.018

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ミリスチン酸はC2C12筋管細胞におけるβ-tubulin量を選択的かつジアシルグリセロールキナーゼδ依存的に増大させる2022

    • Author(s)
      堺弘道,坂根郁夫
    • Organizer
      第95回 日本生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 保存期間がD型及びL型βアミノイソ酪酸の血漿濃度に及ぼす影響2022

    • Author(s)
      外山雄大,野津吉友, 小林弘典, 堺弘道, 國澤研大, 渡辺淳, 矢野彰三, 金崎啓造, 並河徹
    • Organizer
      第47回医用マススペクトル学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ミリスチン酸はC2C12細胞の筋分化過程におけるβ-tubulinの発現量を増大させる2021

    • Author(s)
      堺弘道,坂根郁夫
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] LC-MS/MSによるβアミノイソ酪酸(β-aminoisobutyric acid)鏡像異性体を識別する測定法の検討2021

    • Author(s)
      外山雄大,野津吉友,田中美砂,小林弘典,堺弘道,國澤研大,渡辺淳,並河徹
    • Organizer
      第46回日本医用マススペクトル学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Functional relationship between sphingomyelin synthase- related protein and diacylglycerol kinase δ2020

    • Author(s)
      Chiaki Murakami, Fumi Hoshino, Hiromichi Sakai, Yasuhiro Hayashi, Atsushi Yamashita and Fumio Sakane
    • Organizer
      ASBMB 2020 Annual Meeting Virtual Spotlight Series
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Functional relationship between sphingomyelin synthase-related protein and diacylglycerol kinase δ2020

    • Author(s)
      Chiaki Murakami, Fumi Hoshino, Hiromichi Sakai, Yasuhiro Hayashi, Atsushi Yamashita, Fumio Sakane
    • Organizer
      Annual Meeting of the American Society for Biochemistry and Molecular Biology at Experimental Biology 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] ジアシルグリセロールキナーゼηはmTOR-raptor-脂肪酸合成酵素経路を介してC2C12筋芽細胞の増殖を制御する2020

    • Author(s)
      堺弘道,村上千明,坂根郁夫
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] ジアシルグリセロールキナーゼδとスフィンゴミエリン合成酵素関連タンパク質は機能的に連関する2020

    • Author(s)
      村上千明,星野史規,堺弘道,林康広,山下純,坂根郁夫
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] ジアシルグリセロールキナーゼηはmTORシグナル経路を介してC2C12筋芽細胞の増殖を制御する2020

    • Author(s)
      堺弘道,村上千明,坂根郁夫
    • Organizer
      第62回日本脂質生化学会
    • Related Report
      2020 Research-status Report
  • [Presentation] スフィンゴミエリン合成酵素関連タンパク質とジアシルグリセロールキナーゼδはsterile α motif domainを介して機能的に連関する2020

    • Author(s)
      村上千明,星野史規,堺弘道,林康広,山下純,坂根郁夫
    • Organizer
      第62回日本脂質生化学会
    • Related Report
      2020 Research-status Report
  • [Remarks] 島根大学 総合科学研究支援センター 生体情報・RI実験部門

    • URL

      https://www.med.shimane-u.ac.jp/CRLHP/index.html

    • Related Report
      2021 Research-status Report 2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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