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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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. H-1-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.

Original languageEnglish
Pages (from-to)99-108
Number of pages10
JournalPhysiological Genomics
Issue number2
Publication statusPublished - 24 Apr 2007

Keywords / Materials (for Non-textual outputs)

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


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