A metabonomic comparison of urinary changes in Zucker and GK rats.

A metabonomic comparison of urinary changes in Zucker and GK rats.
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DOI:
10.1155/2010/431894
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发表时间:
2010
影响因子:
--
通讯作者:
Lin DH
Lin DH
中科院分区:
其他
文献类型:
--
作者:
Zhao LC;Zhang XD;Liao SX;Gao HC;Wang HY;Lin DH

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为进一步探讨2型糖尿病(T2 DM)的发病机制和发病过程,采用基于NMR的代谢组学方法,比较了Zucker肥胖大鼠和Goto kakizaki(GK)大鼠的尿代谢谱。两种模型大鼠尿样的主成分分析(PCA)表明,与对照组大鼠相比,肌酸/肌酐、二甲胺和乙酰乙酸水平显著升高,同时柠檬酸盐、2-酮戊二酸盐、乳酸盐、马尿酸盐和琥珀酸盐水平分别下降。同时,与Zucker肥胖大鼠相比,GK大鼠显示出降低的三甲胺、乙酸盐和胆碱水平,以及增加的肌酸/肌酸酐、乙酰乙酸盐、丙氨酸、柠檬酸盐、2-酮戊二酸盐、琥珀酸盐、乳酸盐和马尿酸盐水平。本研究证明了T2 DM两个阶段之间的代谢相似性,包括三羧酸(TCA)循环减少和酮体产生增加。另外,与Zucker肥胖大鼠相比,GK大鼠能量代谢产物浓度增加,表明高血糖阶段能量代谢变化大于胰岛素抵抗阶段。
To further investigate pathogenesis and pathogenic process of type 2 diabetes mellitus (T2DM), we compared the urinary metabolic profiling of Zucker obese and Goto-kakizaki (GK) rats by NMR-based metabonomics. Principal component analysis (PCA) on urine samples of both models rats indicates markedly elevated levels of creatine/creatinine, dimethylamine, and acetoacetate, with concomitantly declined levels of citrate, 2-ketoglurarate, lactate, hippurate, and succinate compared with control rats, respectively. Simultaneously, compared with Zucker obese rats, the GK rats show decreased levels of trimethylamine, acetate, and choline, as well as increased levels of creatine/creatinine, acetoacetate, alanine, citrate, 2-ketoglutarate, succinate, lactate, and hippurate. This study demonstrates metabolic similarities between the two stages of T2DM, including reduced tricarboxylic acid (TCA) cycle and increased ketone bodies production. In addition, compared with Zucker obese rats, the GK rats have enhanced concentration of energy metabolites, which indicates energy metabolic changes produced in hyperglycemia stage more than in insulin resistance stage.
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