期刊
ANALYTICAL BIOCHEMISTRY
卷 383, 期 1, 页码 76-84出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ab.2008.07.041
关键词
Metabolomics; NMR spectroscopy; Type 1 diabetes; TCA cycle; Gluconeogenesis
资金
- National Institutes of Health (NIH)
- Roadmap Initiative on Metabolomics Technology [NIH/NIDDK 3 R21/R33 DK070290-01]
- Collaborative Biomedical Research
- Purdue University/Discovery Park
- Spanish MEC [AGL2005-06726-CO4-03]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R33DK070290, R21DK070290] Funding Source: NIH RePORTER
Type 1 diabetes was induced in Sprague-Dawley rats using streptozotocin. Rat urine samples (8 diabetic and 10 control) were analyzed by H-1 nuclear magnetic resonance (NMR) spectroscopy. The derived metabolites using univariate and multivariate statistical analysis were subjected to correlative analysis. Plasma metabolites were measured by a series of bioassays. A total of 17 urinary metabolites were identified in the H-1 NMR spectra and the loadings plots after principal components analysis. Diabetic rats showed significantly increased levels of glucose (P < 0.00001), alanine (P < 0.0002), lactate (P < 0.05), ethanol (P < 0.05), acetate (P < 0.05), and fumarate (P < 0.05) compared with controls. Plasma assays showed higher amounts of glucose, urea, triglycerides, and thiobarbituric acid-reacting substances in diabetic rats. Striking differences in the Pearson's correlation of the 17 NMR-detected metabolites were observed between control and diabetic rats. Detailed analysis of the altered metabolite levels and their correlations indicate a significant disturbance in the glucose metabolism and tricarboxylic acid (TCA) cycle and a contribution from gut microbial metabolism. Specific perturbed metabolic pathways include the glucosealanine and Cori cycles, the acetate switch, and choline metabolism. Detection of the altered metabolic pathways and bacterial metabolites using this correlative and quantitative NMR-based metabolomics approach should help to further the understanding of diabetes-related mechanisms. (c) 2008 Elsevier Inc. All rights reserved.
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