Systemic and characteristic metabolites in the serum of streptozotocin-induced diabetic rats at different stages as revealed by a 1H-NMR based metabonomic approach
Systemic and characteristic metabolites in the serum of streptozotocin-induced diabetic rats at different stages as revealed by a 1H-NMR based metabonomic approach
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DOI：
10.1039/c3mb70609e
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发表时间：
2014-01-01
影响因子：
--
通讯作者：
Gao, Hongchang
中科院分区：
文献类型：
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作者：
Diao, Chengfeng;Zhao, Liangcai;Gao, Hongchang
糖尿病是一种典型的以碳水化合物、脂质和蛋白质代谢异常为特征的异质性代谢紊乱。研究糖尿病发展过程中代谢途径的变化，有助于了解糖尿病的代谢特征和发病机制。本研究采集糖尿病大鼠和年龄相匹配的对照组在STZ治疗后1周和9周的不同时间点的血清样本。采用基于H-1核磁共振（H-1 NMR）的代谢组学定量分析研究代谢变化。血清样本还进行了临床化学分析，以验证代谢组学观察到的代谢变化。偏最小二乘判别分析（PLS-DA）表明，糖尿病大鼠的血清代谢物水平与对照大鼠不同。这些结果表明，两组在第1周和第9周的代谢特征有显著差异。定量分析显示，糖尿病大鼠体内代谢产物如丙酮酸、乳酸、柠檬酸、丙酮、醋酸酯、醋酸酯、甘油和缬氨酸的水平呈时间依赖性变化。提示糖酵解、三羧酸循环、糖异生、脂肪酸β -氧化、支链氨基酸代谢、酪氨酸代谢等代谢途径的代谢产物参与了糖尿病的发展。代谢变化代表了潜在的特征，并促进了对糖尿病发展机制的更好理解。这项工作进一步表明，H-1核磁共振代谢组学是一种有价值的方法，为糖尿病及其并发症的发病机制提供了新的见解。
Diabetes mellitus is a typical heterogeneous metabolic disorder characterized by abnormal metabolism of carbohydrates, lipids, and proteins. Investigating the changes in metabolic pathways during the evolution of diabetes mellitus may contribute to the understanding of its metabolic features and pathogenesis. In this study, serum samples were collected from diabetic rats and age-matched controls at different time points: 1 and 9 weeks after streptozotocin (STZ) treatment. H-1 nuclear magnetic resonance (H-1 NMR)-based metabonomics with quantitative analysis was performed to study the metabolic changes. The serum samples were also subjected to clinical chemistry analysis to verify the metabolic changes observed by metabonomics. Partial least squares discriminant analysis (PLS-DA) demonstrated that the levels of serum metabolites in diabetic rats are different from those in control rats. These findings indicate that the metabolic characteristics of the two groups are markedly different at 1 and 9 weeks. Quantitative analysis showed that the levels of some metabolites, such as pyruvate, lactate, citrate, acetone, acetoacetate, acetate, glycerol, and valine, varied in a time-dependent manner in diabetic rats. These results suggest that serum metabolites related to glycolysis, the tricarboxylic acid cycle, gluconeogenesis, fatty acid beta-oxidation, branched-chain amino acid metabolism, and the tyrosine metabolic pathways are involved in the evolution of diabetes. The metabolic changes represent potential features and promote a better understanding of the mechanisms involved in the development of diabetes mellitus. This work further suggests that H-1 NMR metabonomics is a valuable approach for providing novel insights into the pathogenesis of diabetes mellitus and its complications.