Piccolo Brian D, Graham James L, Stanhope Kimber L, Fiehn Oliver, Havel Peter J, Adams Sean H
Arkansas Children's Nutrition Center, Little Rock, Arkansas; Department of Pediatrics, University of Arkansas for Medical Science, Little Rock, Arkansas;
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California; Department of Nutrition, University of California, Davis, California;
Am J Physiol Endocrinol Metab. 2016 Jun 1;310(11):E958-69. doi: 10.1152/ajpendo.00052.2016. Epub 2016 Apr 19.
Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasma BCAA and other metabolites were assessed in lean control Sprague-Dawley rats (LC) and temporally during diabetes development in the UCD-T2DM rat model, i.e., prediabetic (PD) and 2 wk (D2W), 3 mo (D3M), and 6 mo (D6M) post-onset of diabetes. Plasma leucine, isoleucine, and valine concentrations were elevated only in D6M rats compared with D2W rats (by 28, 29, and 30%, respectively). This was in contrast to decreased plasma concentrations of several other amino acids in D3M and/or D6M relative to LC rats (Ala, Arg, Glu, Gln, Met, Ser, Thr, and Trp). BCAAs were positively correlated with fasting glucose and negatively correlated with plasma insulin, total body weight, total adipose tissue weight, and gastrocnemius muscle weight in the D3M and D6M groups. Multivariate analysis revealed that D3M and D6M UCD-T2DM rats had lower concentrations of amino acids, amino acid derivatives, 1,5-anhydroglucitol, and conduritol-β-opoxide and higher concentrations of uronic acids, pantothenic acids, aconitate, benzoic acid, lactate, and monopalmitin-2-glyceride relative to PD and D2W UCD-T2DM rats. The UCD-T2DM rat does not display elevated plasma BCAA concentrations until 6 mo post-onset of diabetes. With the acknowledgement that this is a rodent model of T2DM, the results indicate that elevated plasma BCAA concentrations are not necessary or sufficient to elicit an insulin resistance or T2DM onset.
在人类胰岛素抵抗和2型糖尿病（T2DM）中观察到血浆支链氨基酸（BCAAs）浓度升高；然而，关于BCAA表型的被动或因果性质存在一些争议。使用非靶向代谢组学，在瘦对照Sprague-Dawley大鼠（LC）以及UCD-T2DM大鼠模型糖尿病发展过程中（即糖尿病前期（PD）以及糖尿病发病后2周（D2W）、3个月（D3M）和6个月（D6M））对血浆BCAAs和其他代谢物进行了评估。与D2W大鼠相比，仅D6M大鼠的血浆亮氨酸、异亮氨酸和缬氨酸浓度升高（分别升高28%、29%和30%）。这与D3M和/或D6M大鼠相对于LC大鼠几种其他氨基酸的血浆浓度降低形成对比（丙氨酸、精氨酸、谷氨酸、谷氨酰胺、蛋氨酸、丝氨酸、苏氨酸和色氨酸）。在D3M和D6M组中，BCAAs与空腹血糖呈正相关，与血浆胰岛素、总体重、总脂肪组织重量和腓肠肌重量呈负相关。多变量分析显示，相对于PD和D2W UCD-T2DM大鼠，D3M和D6M UCD-T2DM大鼠的氨基酸、氨基酸衍生物、1,5-脱水葡萄糖醇和conduritol-β-氧化物浓度较低，而糖醛酸、泛酸、乌头酸、苯甲酸、乳酸和单棕榈酸甘油酯浓度较高。UCD-T2DM大鼠直到糖尿病发病后6个月才出现血浆BCAA浓度升高。认识到这是一个T2DM啮齿动物模型，结果表明血浆BCAA浓度升高对于引发胰岛素抵抗或T2DM发病既非必要条件也非充分条件。
