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

研究改善葡萄糖、脂质和氨基酸代谢的机制。

• 批准号: 14370022
• 负责人: SHIMOMURA Yoshiharu
• 金额: $ 5.06万
• 依托单位: Nagoya Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370022/
• 关键词: 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

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.

葡萄糖、脂肪酸和氨基酸的代谢是动态相互作用的，这种相互作用对机体系统的整合非常重要。与生活方式有关的疾病在日本越来越普遍。运动对生活方式相关疾病的改善作用已被证实，但其作用机制尚不清楚。在本研究中，我们研究了葡萄糖，脂肪酸和氨基酸代谢的基本调节机制与运动。我们发现：（1）年轻/正常OLETF大鼠骨骼肌中PDK 4的增加和PDP 1的减少是导致PDC活性状态降低的原因，并可能与糖尿病的发生有关;（2）由于抑制支链α-酮酸脱氢酶（BCKDH）激酶活性，促进脂肪酸氧化导致支链氨基酸氧化，（3）BCKDH激酶活性受雌激素的调节;（4）肿瘤坏死因子-a降低BCKDH激酶的结合形式，导致BCKDH复合物活化，促进BCAA氧化。

项目成果

Estrogen controls branched-chain amino acid catabolism in female rats.

• DOI: 10.1093/jn/134.10.2628
• 发表时间: 2004-10
• 期刊: The Journal of nutrition
• 作者: M. Obayashi;Y. Shimomura;N. Nakai;N. Jeoung;M. Nagasaki;T. Murakami;Yuzo Sato;Robert A. Harris

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)

T.Honda 等人：“肝衰竭对大鼠肝脏和肌肉中支链 α-酮酸脱氢酶复合物的影响：急性和慢性的比较”《肝脏病学杂志》40（出版中）。

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

• DOI: 10.1016/j.lfs.2004.04.016
• 发表时间: 2004-09-10
• 期刊: LIFE SCIENCES
• 影响因子: 6.1
• 作者: Bajotto, G;Murakami, T;Sato, Y
• 通讯作者: Sato, Y

Effects of liver failure on the enzymes in the branched-chain amino acid catabolic pathway.

• DOI: 10.1016/j.bbrc.2003.07.022
• 发表时间: 2004-01
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Y. Shimomura;T. Honda;H. Goto;T. Nonami;T. Kurokawa;M. Nagasaki;T. Murakami

Effects of liver failure on branched-chain α-keto acid dehydrogenase complex in rat liver and muscle:: comparison between acute and chronic liver failure

• DOI: 10.1016/j.jhep.2003.11.003
• 发表时间: 2004-03-01
• 期刊: JOURNAL OF HEPATOLOGY
• 影响因子: 25.7
• 作者: Honda, T;Fukuda, Y;Shimomura, Y
• 通讯作者: Shimomura, Y