Potential role of branched-chain amino acids in glucose metabolism through the accelerated induction of the glucose-sensing apparatus in the liver.
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.
Higuchi
Nobito
N
Department of Medicine and Bioregulatory Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
Kato
Masaki
M
Miyazaki
Masayuki
M
Tanaka
Masatake
M
Kohjima
Motoyuki
M
Ito
Tetsuhide
T
Nakamuta
Makoto
M
Enjoji
Munechika
M
Kotoh
Kazuhiro
K
Takayanagi
Ryoichi
R
D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D005941:Glucokinase / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000235:genetics / Q000378:metabolism; D006006:Glycogen Synthase / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
D000597:Amino Acids, Branched-Chain; D051273:Glucose Transporter Type 2; D051780:Sterol Regulatory Element Binding Protein 1; D019298:Glucose-6-Phosphate; D006006:Glycogen Synthase; D005941:Glucokinase; D005947:Glucose