TY - JOUR
T1 - 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
AU - Doisaki, Masao
AU - Katano, Yoshiaki
AU - Nakano, Isao
AU - Hirooka, Yoshiki
AU - Itoh, Akihiro
AU - Ishigami, Masatoshi
AU - Hayashi, Kazuhiko
AU - Goto, Hidemi
AU - Fujita, Yuko
AU - Kadota, Yoshihiro
AU - Kitaura, Yasuyuki
AU - Bajotto, Gustavo
AU - Kazama, Shunsuke
AU - Tamura, Tomohiro
AU - Tamura, Noriko
AU - Feng, Guo Gang
AU - Ishikawa, Naohisa
AU - Shimomura, Yoshiharu
N1 - 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.
PY - 2010/3/5
Y1 - 2010/3/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77649187511&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649187511&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2010.02.004
DO - 10.1016/j.bbrc.2010.02.004
M3 - Article
C2 - 20138840
AN - SCOPUS:77649187511
SN - 0006-291X
VL - 393
SP - 303
EP - 307
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -