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

• Project/Area Number: 14370022
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• Research Institution: Nagoya 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: ¥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)
• Keywords: diabetes / 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.

Research Products

• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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)
• [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)
• [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)