Identification of putative biomarkers for prediabetes by metabolome analysis of rat models of type 2 diabetes

Norihide Yokoi, Masayuki Beppu, Eri Yoshida, Ritsuko Hoshikawa, Shihomi Hidaka, Toshiya Matsubara, Masami Shinohara, Yasuhiro Irino, Naoya Hatano, Susumu Seino

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Biomarkers for the development of type 2 diabetes (T2D) are useful for prediction and intervention of the disease at earlier stages. In this study, we performed a longitudinal study of changes in metabolites using an animal model of T2D, the spontaneously diabetic Torii (SDT) rat. Fasting plasma samples of SDT and control Sprague-Dawley (SD) rats were collected from 6 to 24 weeks of age, and subjected to gas chromatography–mass spectrometry-based metabolome analysis. Fifty-nine hydrophilic metabolites were detected in plasma samples, including amino acids, carbohydrates, sugars and organic acids. At 12 weeks of age, just before the onset of diabetes in SDT rats, the amounts of nine of these metabolites (asparagine, glutamine, glycerol, kynurenine, mannose, n-alpha-acetyllysine, taurine, threonine, and tryptophan) in SDT rats were significantly different from those in SD rats. In particular, metabolites in the tryptophan metabolism pathway (tryptophan and kynurenine) were decreased in SDT rats at 12 weeks of age and later. The lower tryptophan and kynurenine levels in the prediabetic state and later were further confirmed by a replication study on SDT rats and by a longitudinal study on another animal model of T2D, the Otsuka Long-Evans Tokushima Fatty rat. Our data indicate that tryptophan and its metabolites are potential biomarkers for prediabetes and that tryptophan metabolism may be a potential target of intervention for treatment of the disease.

Original languageEnglish
Pages (from-to)1277-1286
Number of pages10
JournalMetabolomics
Volume11
Issue number5
DOIs
Publication statusPublished - Oct 7 2015
Externally publishedYes

Keywords

  • Longitudinal study
  • Metabolomics
  • Plasma biomarkers
  • Rat models
  • Tryptophan
  • Type 2 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

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  • Cite this

    Yokoi, N., Beppu, M., Yoshida, E., Hoshikawa, R., Hidaka, S., Matsubara, T., Shinohara, M., Irino, Y., Hatano, N., & Seino, S. (2015). Identification of putative biomarkers for prediabetes by metabolome analysis of rat models of type 2 diabetes. Metabolomics, 11(5), 1277-1286. https://doi.org/10.1007/s11306-015-0784-9