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Basic studies for development of type 2 diabetes therapy targeting diacylglycerol kinase delta

Research Project

Project/Area Number 25860042
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Research InstitutionChiba University

Principal Investigator

SAKAI Hiromichi  千葉大学, 理学(系)研究科(研究院), 特任研究員 (00375255)

Research Collaborator SAKANE Fumio  千葉大学, 大学院理学研究科, 教授 (10183815)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsジアシルグリセロールキナーゼ / 2型糖尿病 / 薬物療法 / 食餌療法 / ホスファチジン酸 / 脂肪酸
Outline of Final Research Achievements

Decreased expression of diacylglycerol (DAG) kinase (DGK) δ in skeletal muscles is closely related to the pathogenesis of type 2 diabetes. To develop type 2 diabetes therapies targeting DGKδ, we showed that the purified DGKδ expressed DGK activity, indicating that the protein is available for the drug screening, and myristic acid significantly increased DGKδ protein expression and glucose uptake. Moreover, we revealed that DGKδ preferably metabolizes palmitic acid-containing DAG species supplied from phosphatidylcholine-specific phospholipase C pathway in response to high glucose levels.

Report

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

    (34 results)

All 2015 2014 2013 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 5 results,  Acknowledgement Compliant: 5 results) Presentation (24 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Distinct expression and localization of type II diacylglycerol kinase isozymes δ, η and κ in mouse reproductive organs.2015

    • Author(s)
      Shionoya, T., Usuki, T., Komenoi, S., Isozaki, T., Sakai, H., and Sakane, F.
    • Journal Title

      BMC Dev. Biol.

      Volume: 15 Pages: 6-6

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Expression and localization of type II diacylglycerol kinase isozymes δ and η in developing mouse brain2015

    • Author(s)
      Usuki, T., Sakai, H., Shionoya, T., Sato, N. and Sakane, F.
    • Journal Title

      J. Histochem. Cytochem.

      Volume: 63 Issue: 1 Pages: 57-68

    • DOI

      10.1369/0022155414559130

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Diacylglycerol kinase δ phosphorylates phosphatidylcholine-specific phospholipase C-dependent, palmitic acid-containing diacylglycerol species in response to high glucose levels2014

    • Author(s)
      Sakai, H., Kado, S., Taketomi, A. and Sakane, F.
    • Journal Title

      J. Biol. Chem.

      Volume: 289 Issue: 38 Pages: 26607-26617

    • DOI

      10.1074/jbc.m114.590950

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Regulation of diacylglycerol kinase δ expression in C2C12 skeletal muscle cells by free fatty acids2014

    • Author(s)
      Sakiyama, S., Usuki, T., Sakai, H. and Sakane, F.
    • Journal Title

      Lipids

      Volume: 49 Issue: 7 Pages: 633-640

    • DOI

      10.1007/s11745-014-3912-9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] EF-hand motifs of diacylglycerol kinase α interact intra-molecularly with its C1 domains2014

    • Author(s)
      Yamamoto, T., Sakai, H. and Sakane, F.
    • Journal Title

      FEBS Open Bio

      Volume: 4 Issue: 1 Pages: 387-392

    • DOI

      10.1016/j.fob.2014.04.003

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Diacylglycerol kinase γ is a novel anionic phospholipid binding protein with a selective binding preference2014

    • Author(s)
      Takeshita, E., Kume, I., Maeda, Y., Sakai, H. and Sakane, F.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 444 Issue: 4 Pages: 617-621

    • DOI

      10.1016/j.bbrc.2014.01.116

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluations of the selectivities of the diacylglycerol kinase inhibitors R59022 and R59949 among diacylglycerol kinase isozymes using a new non-radioactive assay method2013

    • Author(s)
      Sato, M., Liu, K., Sasaki, S., Kunii, N., Sakai, H., Mizuno, H., Saga, H. and Sakane, F.
    • Journal Title

      Pharmacology

      Volume: 92 Issue: 1-2 Pages: 99-107

    • DOI

      10.1159/000351849

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Osmotic shock-dependent redistribution of diacylglycerol kinase η1 to non-ionic detergent-resistant membrane via the pleckstrin homology and C1 domains2013

    • Author(s)
      Matsutomo, D.
    • Journal Title

      J. Biochem.

      Volume: 153 Issue: 2 Pages: 179-190

    • DOI

      10.1093/jb/mvs130

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] nduction of filopodia-like protrusions by diacylglycerol kinase γ independent of its enzymatic activity in N1E-115 neuroblastoma cells: potential novel function of the catalytic domain of diacylglycerol kinase γ2013

    • Author(s)
      Tanino, F.
    • Journal Title

      Mol. Cell. Biochem.

      Volume: 373 Issue: 1-2 Pages: 85-93

    • DOI

      10.1007/s11010-012-1477-6

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Diacylglycerol kinase δ phosphorylates phosphatidylcholine-specific phospholipase C-dependent, palmitic acid-containing diacylglycerol species in response to high glucose levels2015

    • Author(s)
      Hiromichi Sakai and Fumio Sakane
    • Organizer
      6th international conference on Phospholipase A2 and Lipid Mediators
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-02-10 – 2015-02-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Expression and localization of diacylglycerol kinase δ in the developing mouse brain and phenotype of its brain-specific knockout mice2015

    • Author(s)
      Takako Usuki, Hiromichi Sakai, and Fumio Sakane
    • Organizer
      6th international conference on Phospholipase A2 and Lipid Mediators
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-02-10 – 2015-02-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Diacylglycerol kinase η is a high affinity isozyme for diacylglycerol2015

    • Author(s)
      Suguru Komenoi, Hiromichi Sakai, and Fumio Sakane
    • Organizer
      6th international conference on Phospholipase A2 and Lipid Mediators
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-02-10 – 2015-02-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] ジアシルグリセロールキナーゼδはホスファチジルコリンに由来するパルミチン酸含有ジアシルグリセロール分子種を選択的にリン酸化する2014

    • Author(s)
      堺 弘道,坂根 郁夫
    • Organizer
      第87回日本生化学会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 発達中マウスの脳におけるII型diacylglycerol kinaseアイソザイムδ及びηの発現と局在2014

    • Author(s)
      臼木 貴子,堺 弘道,塩谷 貴生,坂根 郁夫
    • Organizer
      第87回日本生化学会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 雌雄生殖器におけるII型ジアシルグリセロールキナーゼアイソザイム, δ, η, κの発現部位の同定と組織内発現分布の解析2014

    • Author(s)
      塩谷 貴生,臼木 貴子,堺 弘道,坂根 郁夫
    • Organizer
      第87回日本生化学会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] II型ジアシルグリセロールキナーゼのプレクストリン相同ドメインとリン脂質の相互作用2014

    • Author(s)
      久米 愛子,竹下 依那,堺 弘道,坂根 郁夫
    • Organizer
      第87回日本生化学会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cold shock-trigger factor系を用いたジアシルグリセロールキナーゼα, δ, ηの発現・精製と活性測定2014

    • Author(s)
      竹村 文花,米野井 優,佐藤 優里子,堺 弘道,坂根 郁夫
    • Organizer
      第87回日本生化学会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脂質代謝酵素ジアシルグリセロールキナーゼδ,ηの酵素学的性質解析2014

    • Author(s)
      米野井 優,堺 弘道,坂根 郁夫
    • Organizer
      第87回日本生化学会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] ジアシルグリセロールキナーゼδのモノアシルグリセロールキナーゼ活性2014

    • Author(s)
      佐藤 優里子,堺 弘道,水野 悟,坂根 郁夫
    • Organizer
      第87回日本生化学会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 神経分化誘導時に産生されるホスファチジン酸およびリゾホスファチジン酸分子種の解析2014

    • Author(s)
      水野 悟,堺 弘道,坂根 郁夫
    • Organizer
      第87回日本生化学会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] グルコース刺激時におけるジアシルグリセロールキナーゼδのパルミチン酸含有ジアシルグリセロール分子種の選択的代謝2014

    • Author(s)
      堺 弘道,坂根 郁夫
    • Organizer
      第56回日本脂質生化学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-06-06 – 2014-06-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] インスリン抵抗性を制御するDGKδによる糖応答性DG分子種選択的代謝2013

    • Author(s)
      堺 弘道,坂根 郁夫
    • Organizer
      新学術領域「自然炎症」+「脂質マシナリー」合同若手ワークショップ
    • Place of Presentation
      徳島
    • Related Report
      2013 Research-status Report
  • [Presentation] Cell stimulation-dependent phosphorylation/consumption of various diacylglycerol sepecies by diacylglycerol kinase isozymes2013

    • Author(s)
      Fumio Sakane and Hiromichi Sakai
    • Organizer
      The 86th Annual Meeting of the Japanese Biochemical Society
    • Place of Presentation
      Yokohama
    • Related Report
      2013 Research-status Report
  • [Presentation] グルコース刺激時にジアシルグリセロールキナーゼδが代謝するジアシルグリセロール分子種2013

    • Author(s)
      堺 弘道,坂根 郁夫
    • Organizer
      日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Overlay法によるジアシルグリセロールキナーゼδのプレクストリン相同ドメインとリン脂質の相互作用の解析2013

    • Author(s)
      久米 愛子,竹下 依那,堺 弘道,坂根 郁夫
    • Organizer
      日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] インターロイキン-2に応答したジアシルグリセロールキナーゼαの基質選択性の解析2013

    • Author(s)
      水野 悟,堺 弘道,坂根 郁夫
    • Organizer
      日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 脳におけるジアシルグリセロールキナーゼδの発現部位の解明及び脳特異的な本酵素ノックアウトマウスの表現型解析2013

    • Author(s)
      臼木 貴子,堺 弘道,坂根 郁夫
    • Organizer
      日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 脂質代謝酵素ジアシルグリセロールキナーゼδ,ηの大腸菌を利用した大量発現・精製・性質解析2013

    • Author(s)
      米野井 優,斎藤 雅文,堺 弘道,坂根 郁夫
    • Organizer
      日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] ジアシルグリセロールキナーゼη-ノックアウトマウスの表現型の解析2013

    • Author(s)
      磯崎 丈志,臼木 貴子,米野井 優,松友 大介,堺 弘道,坂根 郁夫
    • Organizer
      日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] ジアシルグリセロールキナーゼδの脂肪酸による発現制御2013

    • Author(s)
      崎山 静花,堺 弘道,坂根 郁夫
    • Organizer
      日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] ジアシルグリセロールキナーゼαのCa2+に応答した分子内相互作用解析2013

    • Author(s)
      山本 達也,堺 弘道,坂根 郁夫
    • Organizer
      日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] LC/ESI-MSを用いたホスファチジン酸分子種の定量的分析法の確立とジアシルグリセロールキナーゼαの基質選択性の解析2013

    • Author(s)
      水野 悟,堺 弘道,坂根 郁夫
    • Organizer
      日本脂質生化学会
    • Place of Presentation
      宮城
    • Related Report
      2013 Research-status Report
  • [Presentation] 糖代謝に関わる脂質代謝酵素ジアシルグリセロールキナーゼδの基質選択性の同定

    • Author(s)
      堺 弘道,坂根 郁夫
    • Organizer
      千葉疾患プロテオミクス研究会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Remarks] 千葉大学大学院理学研究科基盤理学専攻生体機能科学研究室ホームページ

    • URL

      http://biofunction.chem.chiba-u.jp/bfc/Top_Page.html

    • Related Report
      2013 Research-status Report

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

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