Altered metabolic signature in Pre-Diabetic NOD Mice
2012 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 4, e35445- p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Public Library of Science , 2012. Vol. 7, no 4, e35445- p.
Endocrinology and Diabetes
IdentifiersURN: urn:nbn:se:umu:diva-54276DOI: 10.1371/journal.pone.0035445ISI: 000305341600149PubMedID: 22514744OAI: oai:DiVA.org:umu-54276DiVA: diva2:517426
This work was supported by the Kempe Foundation, the Medical Faculty at Umeå University, Insamlingsstiftelsen at Umeå University, Magnus Bergvalls stiftelse, JDRF (1-2008-1011), and the Children Diabetes Foundation in Sweden. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.2012-04-232012-04-232016-04-20Bibliographically approved