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Altered Metabolic Signature in Pre-Diabetic NOD Mice

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  • Rasmus Madsen
  • Viqar Showkat Banday
  • Thomas Moritz
  • Johan Trygg
  • Kristina Lejon

Abstract

Altered metabolism proceeding seroconversion in children progressing to Type 1 diabetes has previously been demonstrated. We tested the hypothesis that non-obese diabetic (NOD) mice show a similarly altered metabolic profile compared to C57BL/6 mice. Blood samples from NOD and C57BL/6 female mice was collected at 0, 1, 2, 3, 4, 5, 6, 7, 9, 11, 13 and 15 weeks and the metabolite content was analyzed using GC-MS. Based on the data of 89 identified metabolites OPLS-DA analysis was employed to determine the most discriminative metabolites. In silico analysis of potential involved metabolic enzymes was performed using the dbSNP data base. Already at 0 weeks NOD mice displayed a unique metabolic signature compared to C57BL/6. A shift in the metabolism was observed for both strains the first weeks of life, a pattern that stabilized after 5 weeks of age. Multivariate analysis revealed the most discriminative metabolites, which included inosine and glutamic acid. In silico analysis of the genes in the involved metabolic pathways revealed several SNPs in either regulatory or coding regions, some in previously defined insulin dependent diabetes (Idd) regions. Our result shows that NOD mice display an altered metabolic profile that is partly resembling the previously observation made in children progressing to Type 1 diabetes. The level of glutamic acid was one of the most discriminative metabolites in addition to several metabolites in the TCA cycle and nucleic acid components. The in silico analysis indicated that the genes responsible for this reside within previously defined Idd regions.

Suggested Citation

  • Rasmus Madsen & Viqar Showkat Banday & Thomas Moritz & Johan Trygg & Kristina Lejon, 2012. "Altered Metabolic Signature in Pre-Diabetic NOD Mice," PLOS ONE, Public Library of Science, vol. 7(4), pages 1-9, April.
    • Handle: RePEc:plo:pone00:0035445
    DOI: 10.1371/journal.pone.0035445
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    References listed on IDEAS

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    1. Li, Baibing & Martin, Elaine B. & Morris, A. Julian, 2002. "On principal component analysis in L1," Computational Statistics & Data Analysis, Elsevier, vol. 40(3), pages 471-474, September.
    2. Marko Sysi-Aho & Andrey Ermolov & Peddinti V Gopalacharyulu & Abhishek Tripathi & Tuulikki Seppänen-Laakso & Johanna Maukonen & Ismo Mattila & Suvi T Ruohonen & Laura Vähätalo & Laxman Yetukuri & Tain, 2011. "Metabolic Regulation in Progression to Autoimmune Diabetes," PLOS Computational Biology, Public Library of Science, vol. 7(10), pages 1-16, October.
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    Cited by:

    1. Anders A Bengtsson & Johan Trygg & Dirk M Wuttge & Gunnar Sturfelt & Elke Theander & Magdalena Donten & Thomas Moritz & Carl-Johan Sennbro & Frida Torell & Christian Lood & Izabella Surowiec & Stefan , 2016. "Metabolic Profiling of Systemic Lupus Erythematosus and Comparison with Primary Sjögren’s Syndrome and Systemic Sclerosis," PLOS ONE, Public Library of Science, vol. 11(7), pages 1-15, July.

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