A metabonomic comparison of urinary changes in Zucker and GK rats.
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.
Zhao
Liang-Cai
LC
Shanghai Institute of Materia Medica, The Chinese Academy of Sciences, Shanghai 201203, China.
Zhang
Xiao-Dong
XD
Liao
Shi-Xian
SX
Gao
Hong-Chang
HC
Wang
He-Yao
HY
Lin
Dong-Hai
DH
D000144:Acids, Acyclic / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine*; D003401:Creatine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology* / Q000652:urine*; D004123:Dimethylamines / Q000652:urine; D004195:Disease Models, Animal; D006626:Hippurates / Q000652:urine; D006943:Hyperglycemia / Q000503:physiopathology / Q000652:urine; D007333:Insulin Resistance / Q000502:physiology*; D007657:Ketone Bodies / Q000096:biosynthesis / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics; D015999:Multivariate Analysis; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D013045:Species Specificity; D013654:Taurine / Q000652:urine
D000144:Acids, Acyclic; D015415:Biomarkers; D004123:Dimethylamines; D006626:Hippurates; D007657:Ketone Bodies; D013654:Taurine; C034516:dimethylamine; D003401:Creatine; C030514:hippuric acid