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

Autor: Noriko Tamura, Masatoshi Ishigami, Yasuyuki Kitaura, Hidemi Goto, Tomohiro Tamura, Yuko Fujita, Yoshihiro Kadota, Kazuhiko Hayashi, Shunsuke Kazama, Yoshiaki Katano, Naohisa Ishikawa, Yoshiharu Shimomura, Yoshiki Hirooka, Isao Nakano, Guo-Gang Feng, Masao Doisaki, Akihiro Itoh, Gustavo Bajotto
Rok vydání: 2010
Předmět:
Zdroj: Biochemical and Biophysical Research Communications. 393:303-307
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2010.02.004
Popis: 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 9weeks and hyperglycemic, but not hyperinsulinemic rats aged 18weeks. 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.
Databáze: OpenAIRE
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