Potential role of branched-chain amino acids in glucose metabolism through the accelerated induction of the glucose-sensing apparatus in the liver
✍ Scribed by Nobito Higuchi; Masaki Kato; Masayuki Miyazaki; Masatake Tanaka; Motoyuki Kohjima; Tetsuhide Ito; Makoto Nakamuta; Munechika Enjoji; Kazuhiro Kotoh; Ryoichi Takayanagi
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 695 KB
- Volume
- 112
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
Branched‐chain amino acids (BCAAs) have a potential to improve glucose metabolism in cirrhotic patients; however, the contribution of liver in this process has not been clarified. To estimate the effect of BCAA on glucose metabolism in liver, we evaluated the mRNA expression levels of glucose‐sensing apparatus genes in HepG2 cells and in rat liver after oral administration of BCAA. HepG2 cells were cultured in low glucose (100 mg/dl) or high glucose (400 mg/dl) in the absence or presence of BCAA. The mRNA expression levels and protein levels of GLUT2 and liver‐type glucokinase (L‐GK) were estimated using RT‐PCR and immunoblotting. The expression levels of transcriptional factors, including SREBP‐1c, ChREBP, PPAR‐γm and LXRα, were estimated. The mRNA expression levels of transcriptional factors, glycogen synthase, and genes involved in gluconeogenesis were evaluated in rat liver at 3 h after the administration of BCAA. BCAA accelerated the expression of GLUT2 and L‐GK in HepG2 cells in high glucose. Expression levels of ChREBP, SREBP‐1c, and LXRα were also increased in this condition. BCAA administration enhanced the mRNA expression levels of L‐GK, SREBP‐1c, and LXRα and suppressed the expression levels of G‐6‐Pase in rat liver, without affecting the expression levels of glycogen synthase or serum glucose concentrations. BCAA administration enhanced the bioactivity of the glucose‐sensing apparatus, probably via the activation of a transcriptional mechanism, suggesting that these amino acids may improve glucose metabolism through the accelerated utility of glucose and glucose‐6‐phosphate in the liver. J. Cell. Biochem. 112: 30–38, 2011. © 2010 Wiley‐Liss, Inc.