Regulation of hepatic branched-chain α-keto acid dehydrogenase kinase in a rat model for type 2 diabetes mellitus at different stages of the disease
Regulation of hepatic branched-chain α-keto acid dehydrogenase kinase in a rat model for type 2 diabetes mellitus at different stages of the disease
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DOI：
10.1016/j.bbrc.2010.02.004
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发表时间：
2010-03-05
影响因子：
3.1
通讯作者：
Shimomura, Yoshiharu
中科院分区：
文献类型：
--
作者：
Doisaki, Masao;Katano, Yoshiaki;Shimomura, Yoshiharu
支链α-酮酸脱氢酶（BCKDH）激酶（BDK）是负责调控BCKDH复合物的酶，是支链氨基酸（BCAA）催化过程中的限速酶。在本研究中，我们研究了自发性2型糖尿病肝BDK的表达和活性，使用高胰岛素血症Zucker糖尿病脂肪大鼠9周龄和高血糖，但不是高胰岛素血症大鼠18周龄。肝脏BDK mRNA和总BDK蛋白的丰度与血清胰岛素浓度的变化无关。另一方面，结合到复合物的BDK的量及其激酶活性与血清胰岛素水平的改变相关，表明高胰岛素血症上调肝脏BDK。BDK的活性与BCKDH复合物的活性呈负相关，在高胰岛素血症大鼠中BCKDH复合物的活性受到抑制。这些结果表明，胰岛素通过调节肝脏BDK活性来调节2型糖尿病大鼠的BCAA催化剂。(C)2010年爱思唯尔公司All rights reserved.
Branched-chain alpha-keto acid dehydrogenase (BCKDH) kinase (BDK) is responsible for the regulation of BCKDH complex, which is the rate-limiting enzyme in the catabolism of branched-chain amino acids (BCAAs). In the present study, we investigated the expression and activity of hepatic BDK in spontaneous type 2 diabetes using hyperinsulinemic Zucker diabetic fatty rats aged 9 weeks and hyperglycemic, but not hyperinsulinemic rats aged 18 weeks. The abundance of hepatic BDK mRNA and total BDK protein did not correlate with changes in serum insulin concentrations. On the other hand, the amount of BDK bound to the complex and its kinase activity were correlated with alterations in serum insulin levels, suggesting that hyperinsulinemia upregulates hepatic BDK. The activity of BDK inversely corresponded with the BCKDH complex activity, which was suppressed in hyperinsulinemic rats. These results suggest that insulin regulates BCAA catabolism in type 2 diabetic rats by modulating the hepatic BDK activity. (C) 2010 Elsevier Inc. All rights reserved.