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Physiol. Genomics 29: 99-108, 2007. First published December 26, 2006; doi:10.1152/physiolgenomics.00194.2006
1094-8341/07 $8.00
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Received 5 September 2006; accepted in final form 15 December 2006.
Physiological Genomics 29:99-108 (2007)
1094-8341/07 $8.00 © 2007 American Physiological Society

A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human

R. M. Salek 1,*, M. L. Maguire 1,*, E. Bentley 2, D. V. Rubtsov 1, T. Hough 3, M. Cheeseman 3, D. Nunez 4, B. C. Sweatman 4, J. N. Haselden 4, R. D. Cox 2, S. C. Connor 4 and J. L. Griffin 1

1 Department of Biochemistry, University of Cambridge, Cambridge
2 Mammalian Genetics Unit, Medical Research Council (MRC) Harwell, Oxfordshire
3 The Mary Lyon Centre, MRC Harwell, Harwell, Oxfordshire
4 Safety Assessment, GlaxoSmithKline, Ware, Herts, United Kingdom

Type 2 diabetes mellitus is the result of a combination of impaired insulin secretion with reduced insulin sensitivity of target tissues. There are an estimated 150 million affected individuals worldwide, of whom a large proportion remains undiagnosed because of a lack of specific symptoms early in this disorder and inadequate diagnostics. In this study, NMR-based metabolomic analysis in conjunction with multivariate statistics was applied to examine the urinary metabolic changes in two rodent models of type 2 diabetes mellitus as well as unmedicated human sufferers. The db/db mouse and obese Zucker (fa/fa) rat have autosomal recessive defects in the leptin receptor gene, causing type 2 diabetes. 1H-NMR spectra of urine were used in conjunction with uni- and multivariate statistics to identify disease-related metabolic changes in these two animal models and human sufferers. This study demonstrates metabolic similarities between the three species examined, including metabolic responses associated with general systemic stress, changes in the TCA cycle, and perturbations in nucleotide metabolism and in methylamine metabolism. All three species demonstrated profound changes in nucleotide metabolism, including that of N-methylnicotinamide and N-methyl-2-pyridone-5-carboxamide, which may provide unique biomarkers for following type 2 diabetes mellitus progression.

metabonomics; metabolic syndrome; biofluids; Zucker rat; db/db mouse; nuclear magnetic resonance spectroscopy; leptin resistance




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J. L. Griffin and A. Vidal-Puig
Current challenges in metabolomics for diabetes research: a vital functional genomic tool or just a ploy for gaining funding?
Physiol Genomics, June 1, 2008; 34(1): 1 - 5.
[Abstract] [Full Text] [PDF]


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