Regulation of hepatic branched-chain alpha-keto acid dehydrogenase kinase in a rat model for type 2 diabetes mellitus at different stages of the disease.
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.
Department of Gastroenterology, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Japan.
Masao
M
Doisaki
Yoshiaki
Y
Katano
Isao
I
Nakano
Yoshiki
Y
Hirooka
Akihiro
A
Itoh
Masatoshi
M
Ishigami
Kazuhiko
K
Hayashi
Hidemi
H
Goto
Yuko
Y
Fujita
Yoshihiro
Y
Kadota
Yasuyuki
Y
Kitaura
Gustavo
G
Bajotto
Shunsuke
S
Kazama
Tomohiro
T
Tamura
Noriko
N
Tamura
Guo-Gang
GG
Feng
Naohisa
N
Ishikawa
Yoshiharu
Y
Shimomura
D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology*; D004195:Disease Models, Animal; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker
D000597:Amino Acids, Branched-Chain; D007328:Insulin; D012333:RNA, Messenger; D011494:Protein Kinases; C035627:(3-methyl-2-oxobutanoate dehydrogenase (lipoamide)) kinase