Decreased enzyme activity and contents of hepatic branched-chain α-keto acid dehydrogenase complex subunits in a rat model for type 2 diabetes mellitus
Decreased enzyme activity and contents of hepatic branched-chain α-keto acid dehydrogenase complex subunits in a rat model for type 2 diabetes mellitus
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DOI：
10.1016/j.metabol.2009.04.029
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发表时间：
2009-10-01
影响因子：
9.8
通讯作者：
Shimomura, Yoshiharu
中科院分区：
文献类型：
--
作者：
Bajotto, Gustavo;Murakami, Taro;Shimomura, Yoshiharu
线粒体支链α-酮酸脱氢酶复合体(BCKDC)负责支链氨基酸分解代谢的关键步骤。在本研究中，我们研究了大冢Long-Evans Tokushima Fatty(OLETF)大鼠在2型糖尿病发病前(8周)和之后(25周)BCKDC的调节。以Long-Evans Tokushima Otsuka(LETO)大鼠为对照。青年和中年OLETF大鼠血浆支链氨基酸和支链α-酮酸浓度显著升高。虽然肝脏复合体在所有动物中几乎100%活跃，但在8周龄和25周龄时，OLETF的BCKDC总活性和E1α、E1β和E2亚基的蛋白丰度显著低于LETO大鼠。此外，25周龄LETO大鼠肝脏BCKDC活性和蛋白含量显著低于8周龄LETO大鼠。在骨骼肌中，OLETF大鼠的E_1β和E_2蛋白显著减少，而E_(Ta)则呈增加趋势。综上所述，这些结果提示：(1)OLETF大鼠全身支链α-酮酸氧化能力显著降低，与糖尿病的发展无关；(2)衰老过程使正常大鼠肝脏BCKDC活性和蛋白丰度降低；(3)BCKDC亚单位在骨骼肌中可能存在差异转录后调节。(C)2009 Elsevier Inc.保留所有权利。
The mitochondrial branched-chain a-keto acid dehydrogenase complex (BCKDC) is responsible for the committed step in branched-chain amino acid catabolism. In the present study, we examined BCKDC regulation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats both before (8 weeks of age) and after (25 weeks of age) the onset of type 2 diabetes mellitus. Long-Evans Tokushima Otsuka (LETO) rats Were used as controls. Plasma branched-chain amino acid and branched-chain a-keto acid concentrations were significantly increased in young and middle-aged OLETF rats. Although the hepatic complex was nearly 100% active in all animals, total BCKDC activity and protein abundance of E1 alpha, E1 beta, and E2 Subunits were markedly lower in OLETF than in LETO rats at 8 and 25 weeks of age. In addition, hepatic BCKDC activity and protein amounts were significantly decreased in LETO rats aged 25 weeks than in LETO rats aged 8 weeks. In skeletal Muscle, E1 beta and E2 proteins were significantly reduced, whereas Eta tended to increase in OLETF rats. Taken together, these results Suggest that (1) whole-body branched-chain a-keto acid oxidation capacity is extremely reduced in OLETF rats independently of diabetes development, (2) the aging process decreases BCKDC activity and protein abundance in the fiver of normal rats, and (3) differential postranscriptional regulation for the subunits of BCKDC may exist in skeletal Muscle. (c) 2009 Elsevier Inc. All rights reserved.