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

doi:10.1016/j.bbrc.2010.02.004

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

Research output: Contribution to journal › Article › peer-review

36 Citations (Scopus)

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 language	English
Pages (from-to)	303-307
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	393
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2010.02.004
Publication status	Published - 05-03-2010
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2010.02.004

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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

@article{d1bb1a74dbc64192b874ef277319cd77,

title = "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",

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.",

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

note = "Funding Information: This work was supported in part by a Grant-in-Aid for Scientific Research ( 20658034 to Y.S.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.",

year = "2010",

month = mar,

day = "5",

doi = "10.1016/j.bbrc.2010.02.004",

language = "English",

volume = "393",

pages = "303--307",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Academic Press Inc.",

number = "2",

}

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, GG, 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, vol. 393, no. 2, pp. 303-307. https://doi.org/10.1016/j.bbrc.2010.02.004

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. / Doisaki, Masao; Katano, Yoshiaki; Nakano, Isao et al.
In: Biochemical and Biophysical Research Communications, Vol. 393, No. 2, 05.03.2010, p. 303-307.

Research output: Contribution to journal › Article › peer-review

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

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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