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Development of a novel antidiabetic drug based on the targeting of GnT-IVa glycosyltransferase

Research Project

Project/Area Number 23790363
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionKumamoto University (2013)
Osaka University (2011-2012)

Principal Investigator

OHTSUBO KAZUAKI  熊本大学, 生命科学研究部, 教授 (30525457)

Co-Investigator(Renkei-kenkyūsha) KOREKANE Hiroaki  独立行政法人理化学研究所, 疾患糖鎖研究チーム, 研究員 (50421912)
NAKAJIMA Kazuki  独立行政法人理化学研究所, 神経膜機能研究チーム, 研究員 (10442998)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords糖鎖修飾 / グルコーストランスポーター / グルコースセンサー機能 / 膵臓β細胞 / 糖転移酵素発現調節 / 糖尿病 / 高脂肪食
Research Abstract

We have focused on the physiological and functional regulation mechanism of a glycosyltransferase "GnT-IVa", modulating the glucose sensor function of pancreatic beta cells, for developing a novel antidiabetic drug. We have revealed that high fat-diet induces significant oxidative stress in pancreatic beta cells that can be a trigger to suppress GnT-IVa expression and diminishes glucose stimulated insulin secretion in the pathogenesis of type 2 diabetes. Besides, we engineered to express GnT-IVa in pancreatic beta cells in vivo, and then revealed that they are resistant to the high fat-diet induced diabetes that strongly suggest that GnT-IVa is an important target to develop antidiabetic drugs. We established cell-based assay system for exploring the drug compounds enhancing GnT-IVa expression from chemical libraries.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (21 results)

All 2014 2013 2012 2011 Other

All Journal Article (5 results) (of which Peer Reviewed: 4 results) Presentation (10 results) (of which Invited: 5 results) Book (2 results) Remarks (4 results)

  • [Journal Article] Physiological relevance of protein-glycosylation to pathogenesis of diabetes2014

    • Author(s)
      Kazuaki Ohtsubo Naoyuki Taniguchi
    • Journal Title

      Journal of Physical Fitness and Sports Medicine

      Volume: 3 Pages: 1-6

    • NAID

      130004626100

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-Glycosylation modulates the membrane sub-domain distribution and activity of glucose transporter 2 in pancreatic beta cells2013

    • Author(s)
      Ohtsubo K, Takamatsu S, Gao C, Korekane H, Kurosawa TM, Taniguchi N
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 434(2) Issue: 2 Pages: 346-351

    • DOI

      10.1016/j.bbrc.2013.03.076

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.2013

    • Author(s)
      Rina Takamiya
    • Journal Title

      Glycobiology

      Volume: 23 Issue: 2 Pages: 178-187

    • DOI

      10.1093/glycob/cws139

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 膵臓β細胞のグルコーストランスポーターの糖鎖修飾障害と糖尿病発症2013

    • Author(s)
      大坪和明
    • Journal Title

      実験医学増刊 第三の生命鎖 糖鎖の機能と疾患

      Volume: 31 Pages: 91-97

    • Related Report
      2013 Annual Research Report
  • [Journal Article] A Pathway to Diet- and Obesity-Associated Diabetes Through Attenuation of Pancreatic Beta Cell Glycosylation and Glucose Transport2011

    • Author(s)
      Kazuaki Ohtsubo, Mark Z Chen, Jerrold M Olefsky, Jamey D Marth
    • Journal Title

      Nature Medicine

      Volume: 17 Issue: 9 Pages: 1067-1075

    • DOI

      10.1038/nm.2414

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 糖鎖が紐解く生活習慣病のメカニズム2014

    • Author(s)
      大坪和明
    • Organizer
      応用生命科学研究センター 第5回公開シンポジウム
    • Place of Presentation
      香川 (香川大学)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 糖尿病発症過程におけるβ細胞の糖鎖異常2013

    • Author(s)
      大坪和明
    • Organizer
      Japan Consortium for Glycobiology and Glycotechnology
    • Place of Presentation
      仙台(東北薬科大学)
    • Year and Date
      2013-10-25
    • Related Report
      2013 Final Research Report
  • [Presentation] 膵臓β細胞におけるN型糖鎖修飾によるGLUT2の膜ドメイン局在と機能制御2013

    • Author(s)
      大坪和明、高松真二、高叢笑、是金宏昭、谷口直之
    • Organizer
      日本糖質学会年会
    • Place of Presentation
      大阪(大阪国際交流センター)
    • Year and Date
      2013-08-07
    • Related Report
      2013 Final Research Report
  • [Presentation] 膵臓β細胞におけるN型糖鎖修飾によるGLUT2の膜ドメイン局在と機能制御2013

    • Author(s)
      大坪和明、高松真二、高叢笑、是金宏昭、黒澤努、谷口直之
    • Organizer
      日本糖質学会 年会
    • Place of Presentation
      大阪 (大阪国際交流センター)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 糖尿病発症過程におけるβ細胞の糖鎖異常2013

    • Author(s)
      大坪和明
    • Organizer
      Japan Consortium for Glycobiology and Glycotechnology
    • Place of Presentation
      仙台 (東北薬科大学)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 糖尿病発症過程におけるグルコーストランスポーターの異常2013

    • Author(s)
      大坪和明
    • Organizer
      生理学研究所 研究会 (細胞センサーの分子機構・相互作用・ネットワーク研究会)
    • Place of Presentation
      岡崎 (自然科学研究機構生理学研究所)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 膵β細胞の糖鎖修飾とグルコース輸送低下を介する糖尿病発症経路2012

    • Author(s)
      大坪和明
    • Organizer
      第13回関西グライコサイエンスフォーラム
    • Place of Presentation
      大阪市立大学学術情報総合センター(大阪)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 膵臓β細胞における糖鎖修飾調節を介した血糖コントロール機構2012

    • Author(s)
      大坪和明
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Pathway toDiet–and Obesity–Associated Diabetes Through Attenuation of Pancreatic Beta Cell Glycosylation and Glucose Transport2011

    • Author(s)
      Kazuaki Ohtsubo, Mark Z. Chen, Jerold M. Olefsky and Jamey D. Marth
    • Organizer
      Annual Meeting of Society for Glycobiology
    • Place of Presentation
      Seattle USA
    • Year and Date
      2011-11-11
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト2型糖尿病における膵臓β細胞の糖鎖異常2011

    • Author(s)
      大坪和明
    • Organizer
      第84回日本生化学会大会(招待講演)
    • Place of Presentation
      京都
    • Related Report
      2011 Research-status Report
  • [Book] Sugar Chains2014

    • Author(s)
      Naoyuki Taniguchi, Tadashi Suzuki, Kazuaki Ohtsubo
    • Total Pages
      250
    • Publisher
      Springer
    • Related Report
      2013 Final Research Report
  • [Book] Sugar chains2014

    • Author(s)
      Naoyuki Taniguchi, Tadashi Suzuki, Kazuaki Ohtsubo
    • Total Pages
      250
    • Publisher
      Springer
    • Related Report
      2013 Annual Research Report
  • [Remarks] 理化学研究所プレスリリース

    • URL

      http://www.riken.jp/r-world/info/release/press/2011/110815/detail.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 理化学研究所 プレスリリース

    • URL

      http://www.riken.jp/r-world/info/release/press/2011/110815/detail.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 大阪大学 産業科学研究所 ホームページ

    • URL

      http://www.sanken.osaka-u.ac.jp/jp/organization/dg/dg_index.html

    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.riken.jp/r-world/info/release/press/2011/110815/detail.html

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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