Regulation of branched-chain amino acid catabolism in rat models for spontaneous type 2 diabetes mellitus.
The branched-chain alpha-keto acid dehydrogenase (BCKDH) complex is the most important regulatory enzyme in branched-chain amino acid (BCAA) catabolism. We examined the regulation of hepatic BCKDH complex activity in spontaneous type 2 diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats and Zucker diabetic fatty rats. Hepatic BCKDH complex activity in these rats was significantly lower than in corresponding control rats. The amount of BCKDH complex in OLETF rats corresponded to the total activity of the complex. Activity and abundance of the bound form of BCKDH kinase, which is responsible for inactivation of the complex, showed an inverse correlation to BCKDH complex activity in OLETF rats. Dietary supplementation of 5% BCAAs for 10 weeks markedly increased BCKDH complex activity, and decreased the activity and bound form of BCKDH kinase in the rats. These results suggest that BCAA catabolism in type 2 diabetes is downregulated and enhanced by BCAA supplementation.
Department of Gastroenterology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Teiji
T
Kuzuya
Yoshiaki
Y
Katano
Isao
I
Nakano
Yoshiki
Y
Hirooka
Akihiro
A
Itoh
Masatoshi
M
Ishigami
Kazuhiko
K
Hayashi
Takashi
T
Honda
Hidemi
H
Goto
Yuko
Y
Fujita
Rie
R
Shikano
Yuji
Y
Muramatsu
Gustavo
G
Bajotto
Tomohiro
T
Tamura
Noriko
N
Tamura
Yoshiharu
Y
Shimomura
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000378:metabolism*; D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000378:metabolism*; D004032:Diet; D004195:Disease Models, Animal; D015536:Down-Regulation; D008099:Liver / Q000201:enzymology*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000597:Amino Acids, Branched-Chain; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D002950:Citrate (si)-Synthase; D011494:Protein Kinases; C035627:(3-methyl-2-oxobutanoate dehydrogenase (lipoamide)) kinase