Potential role of branched‐chain amino acids in glucose metabolism through the accelerated induction of the glucose‐sensing apparatus in the liver

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-gm and LXRa, 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 LXRa were also increased in this condition. BCAA administration enhanced the mRNA expression levels of L-GK, SREBP-1c, and LXRa 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.

Effect of branched‑chain amino acid supplementation on insulin resistance and quality of life in chronic hepatitis C patients

“…Albumin production was increased in an indirect manner, indicating that the BCAAs activated hepatic protein synthesis, probably through mTOR (25,48). At present, the role of BCAAs and their implications in the development of IR remain controversial.…”

Oral Branched-Chain Amino Acid Granules Reduce the Incidence of Hepatocellular Carcinoma and Improve Event-Free Survival in Patients with Liver Cirrhosis

“…Kawaguchi et al [33] demonstrated that BCAA supplementation improved insulin resistance in patients with chronic liver disease. Several in vivo studies revealed that the mechanisms underlying this effect include enhanced glucose uptake by skeletal muscle, adipocytes and hepatocytes [34,35,36]. These results prompted us to consider that the improvements in insulin resistance induced by BCAA supplementation play an important role in suppressing liver carcinogenesis.…”

Branched-chain amino acids in liver diseases

“…In the liver, BCAAs increase the liver X receptor/sterol regulatory element binding protein-1c pathway and subsequently activate liver-type glucokinase and glucose transporter. Furthermore, BCAAs suppress hepatic expression of glucose-6-phosphatase [23] . In adipose tissue, leucine increases insulin-induced phosphorylation of Akt and mTOR, increasing glucose uptake [24] .…”