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Study on the mechanisms responsible for improvement of glucose, lipid, and amino acid metabolism.

Research Project

Project/Area Number 14370022
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology (including Physical medicine and Nutritional physiology)
Research InstitutionNagoya Institute of Technology

Principal Investigator

SHIMOMURA Yoshiharu  Nagoya Institute of Technology, Graduate School of Technology, Professor, 工学研究科, 教授 (30162738)

Co-Investigator(Kenkyū-buntansha) MURAKAMI Taro  Nagoya Institute of Technology, Graduate School of Technology, Associate Professor, 工学研究科, 助教授 (10252305)
長崎 大  愛知学院大学, 心身科学部, 助手 (30387568)
小竹 克博  愛知医科大学, 医学部, 助手 (50351101)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥3,800,000 (Direct Cost: ¥3,800,000)
Keywordsdiabetes / insulin resistance / glucose metabolism / branched-chain amino acid metabolism / fatty acid metabolism / pyruvate dehydrogenase / branched-chain α-keto acid dehydroqenase / ラット / BCKDH複合体 / BCKDH kinase / PDH複合体 / PDH kinase / 性差 / OLETFラット / 分岐鎖アミノ酸 / クロフィブラート / PPARα / 急性肝炎 / 肝硬変 / pyruvate dehydrogenase complex / 自然発症糖尿病 / インスリン抵抗性 / 血清遊離脂肪酸 / LETOラット
Research Abstract

The metabolism of glucose, fatty acids, and amino acids are dynamically interacted, and the interaction is very important in integration of the body system. The life-style-related diseases are getting common in Japan. It is evident that exercise is very effective to improve the life-style-related diseases, but the mechanisms are not so clear. In the present study, we have investigated the basic regulatory mechanisms of glucose, fatty acid, and amino acid metabolism in relation to exercise. We found that (1)greater PDK4 and less PDP1 in skeletal muscle of young/normal OLETF rats are responsible for the lowering of the PDC activity state and may be related with the development of diabetes mellitus, (2)promotion of fatty acid oxidation resulted in oxidation of branched-chain amino acids due to suppression of branched-chain α-keto acid dehydrogenase(BCKDH) kinase activity, (3)BCKDH kinase activity was regulated by estrogen, and (4)tumor-necrosis factor-a decreased the bound form of BCKDH kinase, resulting in activation of BCKDH complex and promotion of BCAA oxidation.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (18 results)

All 2005 2004 2002 Other

All Journal Article (15 results) Publications (3 results)

  • [Journal Article] Activation of hepatic branched-chain α-keto acid dehydrogenase complex by tumor necrosis factor-α in rats.2005

    • Author(s)
      Shiraki, M., et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 328

      Pages: 973-978

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Activation of hepatic branched-chain α-keto acid dehydrogenase complex by tumor necrosis factor-α in rats.2005

    • Author(s)
      Shiraki, M., Shimomura, Y., Miwa, Y., Fukushima, H., Murakami, T., Tamura, T., Tamura, N., Moriwaki, H.
    • Journal Title

      Biochem.Biophys.Res.Commun. 328

      Pages: 973-978

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of liver failure on the enzymes in the branched-chain amino acid catabolic pathway.2004

    • Author(s)
      Shimomura, Y., et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 313

      Pages: 381-385

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Downregulation of the skeletal muscle pyruvate dehydrogenase complex in the Otsuka Long-Evans Tokushima fatty rat both before and after the onset of diabetes mellitus.2004

    • Author(s)
      Bajotto, G., et al.
    • Journal Title

      Life Sci. 75

      Pages: 2117-2130

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulation of branched-chain amino acid metabolism and pharmacological effects of branched-chain amino acids.2004

    • Author(s)
      Shimomura, Y., et al.
    • Journal Title

      Hepatol.Res. 30S

      Pages: 3-8

    • NAID

      10015455326

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of liver failure on the enzymes in the branched-chain amino acid catabolic pathway.2004

    • Author(s)
      Shimomura, Y., Honda, T., Goto, H., Nonami, T., Kurokawa, T., Nagasaki, M., Murakami, T.
    • Journal Title

      Biochem.Biophys.Res.Commun. 313

      Pages: 381-385

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of liver failure on branched-chain α-keto acid dehydrogenase complex in rat liver and muscle : comparison between acute and chronic liver failure.2004

    • Author(s)
      Honda, T., Fukuda, Y., Nakao, I., Katano, Y., Goto, H., Nagasaki, M., Sato, Y., Murakami, T., Shimomura, Y.
    • Journal Title

      J.Hepatol. 40

      Pages: 439-445

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Downregulation of the skeletal muscle pyruvate dehydrogenase complex in the Otsuka Long-Evans Tokushima fatty rat both before and after the onset of diabetes mellitus.2004

    • Author(s)
      Bajotto, G., Murakami, T., Nagasaki, M., Tamura, T., Tamura, N., Harris, R.A., Shimomura, Y., Sato, Y.
    • Journal Title

      Life Sci. 75

      Pages: 2117-2130

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulation of branched-chain amino acid metabolism and pharmacological effects of branched-chain amino acids.2004

    • Author(s)
      Shimomura, Y., Murakami, T., Nagasaki, M., Honda, T., Goto, H., Kotake, K., Kurokawa, T., Nonami, T.
    • Journal Title

      Hepatol.Res. 30S

      Pages: 3-8

    • NAID

      10015455326

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Estrogen controls branched-chain amino acid catabolism in female rats.2004

    • Author(s)
      M.Obayashi, Y.Shimomura, et al.
    • Journal Title

      Journal of Nutrition 134

      Pages: 2628-2633

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Activation of hepatic branched-chain α-keto acid dehydrogenase complex by tumor necrosis factor-α in rats.2004

    • Author(s)
      M.Shiraki, Y.Shimomura, et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 328

      Pages: 973-978

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of branched-chain amino acid metabolism and pharmacological effects of branched-chain amino acids.2004

    • Author(s)
      Y.Shimomura, et al.
    • Journal Title

      Hepatology Research 30S

    • NAID

      10015455326

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Downregulation of the skeletal muscle pyruvate dehydrogenase complex in the Otsuka Long-Evans Tokushima Fatty rat both before and after the onset of diabetes mellitus.2004

    • Author(s)
      G.Bajotto, Y.Shimomura, et al.
    • Journal Title

      Life Sciences 75

      Pages: 2117-2130

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Clofibric acid stimulates branched-chain amino acid catabolism by three mechanisms.2002

    • Author(s)
      Kobayashi, R., et al.
    • Journal Title

      Arch.Biochem.Biophys. 407

      Pages: 231-240

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clofibric acid stimulates branched-chain amino acid catabolism by three mechanisms.2002

    • Author(s)
      Kobayashi, R., Murakami, T., Obayashi, M., Nakai, N., Jaskiewicz, J., Fujiwara, Y., Shimomura, Y., Harris, R.A.
    • Journal Title

      Arch.Biochem.Biophys. 407

      Pages: 231-240

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] R.Kobayashi, et al.: "Clofibric acid stimulates branched-chain amino acid catabolism by three mechanisms"Archives of Biochemistry and Biophysics. 407. 231-240 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Shimomura, et al.: "Effects of liver failure on the enzymes in the branched-chain amino acid catabolic pathway"Biochemical and Biophysical Research Communications. 313. 381-385 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Honda, et al.: "Effects of liver failure on branched-chain α-keto acid dehydrogenase complex in rat liver and muscle : comparison between acute and chro"Journal of Hepatology. 40(In press). (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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