Zhang Wenlu, Wu Yu'e, Fan Wei, Chen Hongmei, Du Hongli, Rao Junhua
School of Biological and Biological Engineering South China University of Technology Guangzhou China.
Guangdong Key Laboratory of Laboratory Animals Guangzhou China.
Animal Model Exp Med. 2018 Nov 13;1(4):305-313. doi: 10.1002/ame2.12038. eCollection 2018 Dec.
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 gene in Goto-Kakizaki (GK) rats during type 2 diabetes (T2D) progression.
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 and , which encode the rate-limiting enzymes in catabolism of, respectively, branched chain amino acids and branched chain α-keto acid dehydrogenase kinase.
In this study, we showed that GK rat BCAA concentrations were significantly reduced at 4 and 8 weeks ( < 0.05 and < 0.01, respectively), while the expression of 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 (< 0.01), but significantly increased in T2D humans ( < 0.001).
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 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.
本研究旨在测定不同物种中支链氨基酸（BCAA）的浓度，并检测2型糖尿病（T2D）进展过程中Goto-Kakizaki（GK）大鼠肝脏基因的表达模式。
我们通过液相色谱串联质谱法测量了GK大鼠、诱导型T2D食蟹猴和T2D患者体内BCAA的浓度，并使用实时定量PCR分析了分别编码支链氨基酸和支链α-酮酸脱氢酶激酶分解代谢限速酶的 和 的基因表达。
在本研究中，我们发现GK大鼠在4周和8周时BCAA浓度显著降低（分别为 < 0.05和 < 0.01），而GK大鼠肝脏中 在4周和8周时表达增加（分别为1.62倍和1.93倍）。饮食诱导的T2D食蟹猴体内BCAA浓度显著降低（< 0.01），但T2D患者体内BCAA浓度显著升高（< 0.001）。
我们的结果表明，在不同物种以及T2D进展的不同时期，BCAA浓度在不同时间和不同程度上发生变化，三种物种中BCAA浓度的显著变化表明BCAA可能参与了T2D的进展。结果表明，GK大鼠肝脏中 表达增加可能部分解释了4周和8周时血浆BCAA浓度降低的原因。需要进一步研究来探讨非肥胖T2D中BCAA变化的确切机制。
