Abstract
BACKGROUND: This study was conducted to measure the concentration of branched chain amino acid (BCAA) in different species and detect the expression pattern of the liver Bckdha gene in Goto-Kakizaki (GK) rats during type 2 diabetes (T2D) progression. METHODS: We measured the concentration of BCAA in GK rats, induced T2D cynomolgus monkeys and T2D humans by liquid chromatography tandem mass spectrometry, and used real-time quantitative PCR to analyze the gene expression of Bckdha and Bckdk, which encode the rate-limiting enzymes in catabolism of, respectively, branched chain amino acids and branched chain α-keto acid dehydrogenase kinase. RESULTS: In this study, we showed that GK rat BCAA concentrations were significantly reduced at 4 and 8 weeks (P < 0.05 and P < 0.01, respectively), while the expression of Bckdha in GK rat liver was increased at 4 and 8 weeks (1.62-fold and 1.93-fold, respectively). The BCAA concentrations were significantly reduced in diet-induced T2D cynomolgus monkeys (P < 0.01), but significantly increased in T2D humans (P < 0.001). CONCLUSIONS: Our results showed that BCAA concentrations changed at different times and by different amounts in different species and during different periods of T2D progress, and the significant changes of BCAA concentration in the three species indicated that BCAA might participate in the progress of T2D. The results suggested that the increased expression of Bckdha in GK rat liver might partially explain the reduced plasma BCAA concentration at 4 and 8 weeks. Further studies are required to investigate the exact mechanism of BCAA changes in non-obese T2D.