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

Masao Doisaki, Yoshiaki Katano, Isao Nakano, Yoshiki Hirooka, Akihiro Itoh, Masatoshi Ishigami, Kazuhiko Hayashi, Hidemi Goto, Yuko Fujita, Yoshihiro Kadota, Yasuyuki Kitaura, Gustavo Bajotto, Shunsuke Kazama, Tomohiro Tamura, Noriko Tamura, Guo Gang Feng, Naohisa Ishikawa, Yoshiharu Shimomura

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Abstract

Branched-chain α-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.

Original languageEnglish
Pages (from-to)303-307
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume393
Issue number2
DOIs
Publication statusPublished - 05-03-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Doisaki, M., Katano, Y., Nakano, I., Hirooka, Y., Itoh, A., Ishigami, M., Hayashi, K., Goto, H., Fujita, Y., Kadota, Y., Kitaura, Y., Bajotto, G., Kazama, S., Tamura, T., Tamura, N., Feng, G. G., Ishikawa, N., & Shimomura, Y. (2010). 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. Biochemical and Biophysical Research Communications, 393(2), 303-307. https://doi.org/10.1016/j.bbrc.2010.02.004