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Study of protective effects and transcriptional regulation by a novel fatty acid receptor in pancreatic beta cells: its implication in lipotoxicity and glucose intolerance

Research Project

Project/Area Number 23791029
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Metabolomics
Research InstitutionKyoto University

Principal Investigator

TOMITA Tsutomu  京都大学, 医学研究科, 非常勤講師 (50402897)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsGPR40 / 脂肪毒性 / 糖尿病 / 耐糖能異常 / レプチン / 遊離脂肪酸 / インスリン分泌 / 膵島機能調節 / 糖尿病治療薬 / 創薬標的
Research Abstract

To explore the significance of GPR40 in leptin deficiency, GPR40 mRNA expression was assessed in pancreatic islets of genetically obese leptin-deficient rats (Lepmkyo/mkyo), which were established by our laboratory. Body weight of Lepmkyo/mkyowas increased an age-dependent manner. Hypertriglyceridimia and glucose intorelance were worsened in parralell with the progression of obesity. After the age of ~52 weeks, body weight of Lepmkyo/mkyowas decreased and they dead around the age of 60 weeks. Liver lipid concentration and blood transaminase were markedly increased in Lepmkyo/mkyo, suggesting involvement of liver failure in the death of Lepmkyo/mkyo. Fasting insulin levels were markedly increased in Lepmkyo/mkyo, and beta cell area was markedly increased. In contrast, early insulin response after glucose load was markedly decreased. GPR40 mRNA levels were decreased in pancreatic islets of Lepmkyo/mkyo, suggesting possible involvement of GPR40 in insulin secretion in leptin deficient obesity-associated glucose intolerance.

Report

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

    (18 results)

All 2012 2011 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (17 results)

  • [Journal Article] GPR119 expression in normal human tissues and islet cell tumors: evidence for its isletgastrointestinal distribution, expression in pancreatic beta and alpha cells, and involvement in islet function.2012

    • Author(s)
      T. Tomita
    • Journal Title

      Metabolism

      Volume: 62(1) Pages: 70-8

    • NAID

      120005242664

    • URL

      http://dx.doi.org/10.1016/j.metabol.2012.06.010

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] Clinical Implications of G Protein-Coupled Lipid Receptors, GPR40 and GPR119,9thInternational Diabetes Federation Western Pacific Region Congress2012

    • Author(s)
      T. Tomita, 他
    • Organizer
      4thScientific Meeting of the Asian Association for the Study of Diabetes
    • Place of Presentation
      京都市
    • Year and Date
      2012-11-25
    • Related Report
      2012 Final Research Report
  • [Presentation] G 蛋白共役型-中・長鎖脂肪酸受容体GPR40の遺伝性肥満モデルの膵島での発現調節2012

    • Author(s)
      冨田努, 他
    • Organizer
      第33回日本肥満学会
    • Place of Presentation
      京都市
    • Year and Date
      2012-10-12
    • Related Report
      2012 Final Research Report
  • [Presentation] 新規のG蛋白共役型-脂質受容体群GPR40、GP119の臨床的意義2012

    • Author(s)
      冨田努, 他.
    • Organizer
      第55回日本糖尿病学会学術集会
    • Place of Presentation
      横浜市
    • Year and Date
      2012-05-17
    • Related Report
      2012 Final Research Report
  • [Presentation] G 蛋白共役型-脂質受容体GPR119 の臨床的意義:ヒト膵島およびインスリノーマにおける遺伝子発現と膵島機能との連関2012

    • Author(s)
      冨田努, 他.
    • Organizer
      第85回日本内分泌学会学術総会
    • Place of Presentation
      名古屋市
    • Year and Date
      2012-04-21
    • Related Report
      2012 Final Research Report
  • [Presentation] 新規のインスリン分泌促進因子GPR40の遺伝性肥満モデルの発現調節と機能的意義2012

    • Author(s)
      冨田努, 他
    • Organizer
      第85回日本内分泌学会学術総会
    • Place of Presentation
      名古屋市
    • Year and Date
      2012-04-19
    • Related Report
      2012 Final Research Report
  • [Presentation] 新規のインスリン分泌調節因子GPR40の遺伝性肥満モデルでの発現調節と機能的意義2012

    • Author(s)
      冨田努, 他.
    • Organizer
      第109回日本内科学会
    • Place of Presentation
      京都市
    • Year and Date
      2012-04-13
    • Related Report
      2012 Final Research Report
  • [Presentation] G 蛋白共役型-脂肪酸受容体GPR40の遺伝性肥満モデルの膵島での発現調節2011

    • Author(s)
      冨田努, 他.
    • Organizer
      第32回日本肥満学会学術集会
    • Place of Presentation
      淡路市
    • Year and Date
      2011-09-24
    • Related Report
      2012 Final Research Report
  • [Presentation] 膵β細胞に高発現し、中・長鎖脂肪酸をリガンドするG蛋白共役型受容体GPR40の遺伝性肥満モデルの膵島での発現調節2011

    • Author(s)
      冨田努, 他
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2011-05-21
    • Related Report
      2012 Final Research Report
  • [Presentation] 新規のインスリン分泌調節因子GPR40の遺伝子肥満モデルでの発現調節2011

    • Author(s)
      冨田努, 他
    • Organizer
      第84回日本内分泌学会学術総会
    • Place of Presentation
      淡路市
    • Year and Date
      2011-04-21
    • Related Report
      2012 Final Research Report
  • [Presentation] 膵β細胞に高発現し、中・長鎖脂肪酸をリガンドするG蛋白共役型受容体GPR40の遺伝性肥満モデルの膵島での発現調節2011

    • Author(s)
      冨田努, 細田公則, 小鳥真司, 孫徹, 藤倉純二, 岩倉浩, 野口倫生, 森栄作, 内藤雅喜, 吉良友里, 日下部徹, 海老原健, 益崎裕章, 中尾一和
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      札幌プリンスホテル(北海道)
    • Related Report
      2011 Research-status Report
  • [Presentation] G蛋白共役型-脂肪酸受容体GPR40の遺伝性肥満モデルの膵島での発現調節2011

    • Author(s)
      冨田努, 細田公則, 小鳥真司, 孫 徹, 藤倉純二, 岩倉浩, 野口倫生, 日下部徹, 海老原健, 中尾一和
    • Organizer
      第32回日本肥満学会学術集会
    • Place of Presentation
      兵庫県立淡路夢舞台国際会議場(兵庫県)
    • Related Report
      2011 Research-status Report
  • [Presentation] 新規のインスリン分泌調節因子GPR40の遺伝性肥満モデルでの発現調節と機能的意義

    • Author(s)
      冨田努、細田公則、小鳥真司、孫徹、藤倉純二、岩倉浩、野口倫生、日下部徹、海老原健、中尾一和
    • Organizer
      第109回日本内科学会
    • Place of Presentation
      みやこめっせ(京都府)
    • Related Report
      2012 Annual Research Report 2011 Research-status Report
  • [Presentation] 新規のインスリン分泌促進因子GPR40の遺伝性肥満モデルの発現調節と機能的意義

    • Author(s)
      冨田努、細田公則、小鳥真司、孫徹、藤倉純二、岩倉浩、野口倫生、日下部徹、海老原健、中尾一和
    • Organizer
      第85回日本内分泌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] G 蛋白共役型-脂質受容体GPR119 の臨床的意義:ヒト膵島およびインスリノーマにおける遺伝子発現と膵島機能との連関

    • Author(s)
      冨田努、細田公則、小鳥真司、孫徹、藤倉純二、岩倉浩、野口倫生、日下部徹、海老原健、中尾一和
    • Organizer
      第85回日本内分泌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 新規のG蛋白共役型-脂質受容体群GPR40、GP119の臨床的意義

    • Author(s)
      冨田努、細田公則、小鳥真司、藤倉純二、日下部徹、海老原健、中尾一和
    • Organizer
      第55回日本糖尿病学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] G 蛋白共役型-中・長鎖脂肪酸受容体GPR40の遺伝性肥満モデルの膵島での発現調節

    • Author(s)
      冨田努、細田公則、小鳥真司、藤倉純二、日下部徹、海老原健、中尾一和
    • Organizer
      第33回日本肥満学会
    • Place of Presentation
      ホテルグランヴィア京都(京都府)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Clinical Implications of G Protein-Coupled Lipid Receptors, GPR40 and GPR119

    • Author(s)
      T. Tomita, K. Hosoda, S. Odori, J. Fujikura, T. Kusakabe, K. Ebihara, K. Nakao
    • Organizer
      9thInternational Diabetes Federation Western Pacific Region Congress, 4thScientific Meeting of the Asian Association for the Study of Diabetes,
    • Place of Presentation
      京都国際会館(京都府)
    • Related Report
      2012 Annual Research Report

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

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