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新規の膵B細胞機能・増殖・再生調節機構としての脂肪酸-GPR40シグナルの意義

Research Project

Project/Area Number 19659237
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Endocrinology
Research InstitutionKyoto University

Principal Investigator

中尾 一和  Kyoto University, 医学研究科, 教授 (00172263)

Co-Investigator(Kenkyū-buntansha) 細田 公則  京都大学, 医学研究科, 講師 (40271598)
益崎 裕章  京都大学, 医学研究科, 助教 (00291899)
海老原 健  京都大学, 医学研究科, 講師 (70362514)
藤倉 純二  京都大学, 医学研究科, 助教 (70378743)
岩倉 浩  京都大学, 医学研究科, 助教 (20378615)
Project Period (FY) 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2007: ¥3,200,000 (Direct Cost: ¥3,200,000)
Keywordsβ細胞 / GPR40 / インスリン分泌 / 糖尿病
Research Abstract

2型糖尿病の発症におけるGPR40の意義を解明する目的で、遺伝性肥満Koletskyラット(fak/fak)で肥満の進行とともに糖尿病を発症する過程におけるGPR40の意義を検討した。
6週齢ではfak/fakと非肥満対照(+/+)で体重に有意な差がなく、空腹時血中インスリン濃度はfak/fakで+/+と比べ著明(約8倍)に上昇していたが(P<0.0l)、空腹時血糖や糖負荷試験(ipGTT)での血糖に2群間でほとんど差はなかった。このとき、fak/fakの膵島でのGPR40 mRNA発現レベルは+/+とほぼ同等であった。10、14週齢でfak/fakでは+/+と比べ体重が有意に増加していた(P<0.05)。これらの週齢でのipGTTの結果からfak/fakで+/+に比べ耐糖能悪化の進展が示された。経腹腔ブドウ糖負荷試験(ipGTT)で血中インスリン濃度のPeakは、+/+では6、10、14週齢で30分であるのに対して、fak/fakでは6週齢で30分、10週齢で60分、14週齢で90分へと遅延した。fak/fakの膵島GPR40 mRNA発現は10週齢、14週齢では+/+のそれぞれ約1/2、1/3と著明な低下を認めた(P<0.01)。一方、+/+の膵島におけるGPR40 mRNA発現は6週齢から10週齢、14週齢の間でほとんど変化がなかった。さらにfak/fakの10週齢から4週間fak/fakで50%のカロリー制限を行ったところ、体重の増加は抑制され、+/+の体重とほぼ同等になり、ipGTTで耐糖能はほぼ正常化し、血中インスリン濃度のPeakは30分になり、正常化したが、14週齢での膵島GPR40 mRNA発現も+/+と同等にほぼ正常化していた。肥満の進行とともに生じるインスリン分泌異常と耐糖能異常において膵島GPR40遺伝子発現の低下の関与が示唆された。

Report

(1 results)
  • 2007 Annual Research Report
  • Research Products

    (16 results)

All 2007

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (3 results)

  • [Journal Article] Genetic and pharmacological inhibition of Rho-associated kinase II enhances adipogenesis.2007

    • Author(s)
      M. Noguch, K. Nakao, et. al.
    • Journal Title

      J Biol Chem. 282

      Pages: 29574-29583

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Central Melanocortin Signaling Restores Skeletal Muscle AMP-Activated Protein Kinase Phosphorylation in Mice Fed a High-Fat Diet.2007

    • Author(s)
      T. Tanaka, K. Nakao, et. al.
    • Journal Title

      Cell Metab. 5(5)

      Pages: 395-402

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rbp-j regulates expansion of pancreatic epithelial cells and their differentiation into exocrine cells during mouse development.2007

    • Author(s)
      J. Fujikura, K. Nakao, et. al.
    • Journal Title

      Dev Dyn. 236

      Pages: 2779-2791

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Case of Secretin-responsive Insulinoma with Low Serum C-peptide Levels.2007

    • Author(s)
      J. Fujikura, K. Nakao, et. al.
    • Journal Title

      Endocr J. 54(1)

      Pages: 113-121

    • NAID

      10019479541

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptinactions in patients with generalized lipodystrophy.2007

    • Author(s)
      K. Ebihara, K. Nakao, et. al.
    • Journal Title

      J Clin Endocrinol Metab. 92(2)

      Pages: 532-541

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A simple measurement method of visceral fat accumulation by bioelectrical impedance analysis.2007

    • Author(s)
      T. Shiga, K. Nakao, et. al.
    • Journal Title

      ICEBI 2007, IFMBE Proceedings 17

      Pages: 687-690

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ceramide and AMP-activated Protein Kinase are Two Novel Regulators of 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Expression and Activity in Cultured Preadipocytes.2007

    • Author(s)
      N. Arai, K. Nakao, et. al.
    • Journal Title

      Endocrinology 148

      Pages: 5268-5277

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of ghrelin administration on decreased growth hormone status in obese animals.2007

    • Author(s)
      H. Iwakura, K. Nakao, et. al.
    • Journal Title

      Am J Physiol Endocrinol Metab. 293

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Images in cardiovascular medicine. Mitochondrial cardiomyopathy evaluated with cardiac magnetic resonance.2007

    • Author(s)
      M. Nakanishi, K. Nakao, et. al.
    • Journal Title

      Circulation. 116(2)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bezafibrate regulates the expression and enzyme activity of 11beta-hydroxysteroid dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes.2007

    • Author(s)
      S. Nakano, K. Nakao, et. al.
    • Journal Title

      Am J Physiol Endocrinol Metab. 292(4)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Augmentation of 11β-hydroxysteroid dehydrogenase type 1 in LPS-activated J774.1 macrophages? Role of 11β-HSD1 in pro-inflammatory properties in macrophages.2007

    • Author(s)
      T. Ishii, K. Nakao, et. al.
    • Journal Title

      FEBS Lett. 6;581(3)

      Pages: 349-354

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Acute Activation of 5'-AMP-Activated Protein Kinase on Glycogen Regulation in Isolated Rat Skeletal Muscle.2007

    • Author(s)
      Miyamoto, K. Nakao, et. al.
    • Journal Title

      J Appl Physiol. 102(3)

      Pages: 1007-1013

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-fat diet impairs the effects of a single bout of endurance exercise on glucose transport and insulin sensitivity in rat skeletal muscle.2007

    • Author(s)
      S. Tanaka, K. Nakao, et. al.
    • Journal Title

      Metabolism. 56(12)

      Pages: 1719-1728

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] メタボリック症候群モデルKoletskyラット膵島における模型脂肪酸受容体GPR40の遺伝子発現調節とその病態生理的意義2007

    • Author(s)
      冨田 努, 中尾一和, その他
    • Organizer
      第50回日本糖尿病学会年次学術集会
    • Place of Presentation
      仙台
    • Related Report
      2007 Annual Research Report
  • [Presentation] 遺伝性肥満モデルKoletskyラットの糖代謝異常発症過程における模型脂肪酸受容体GPR40の膵島での遺伝子発現調節:その病態生理的意義に関する考察2007

    • Author(s)
      冨田 努, 中尾一和, その他
    • Organizer
      第80回日本内分泌学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2007 Annual Research Report
  • [Presentation] メタボリックシンドロームと脂肪毒性2007

    • Author(s)
      細田公則, 中尾一和, その他
    • Organizer
      第44回日本臨床分子医学会学術集会
    • Place of Presentation
      和歌山
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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