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.
Highlights
Type 1 diabetes is an autoimmune disease which in contrast to the majority of other autoimmune diseases arises already at young age [1]
It has previously been demonstrated that children with genetic predisposition for T1D development and that progressed to T1D display an altered serum metabolic profile compared to the group of non-progressors [3]
We found that non-obese diabetic (NOD) mice display a substantial altered metabolism compared to B6 already as a newborn and this difference was maintained throughout the 15 weeks analyzed
Summary
Type 1 diabetes is an autoimmune disease which in contrast to the majority of other autoimmune diseases arises already at young age [1]. The pathogenesis process in diabetes is so far only detectable as either the appearance of islet-specific autoantibodies and/or the mononuclear infiltration in the islets of Langerhan’s, it is evident that this process is preceded by other molecular and cellular events, which in turn could be reflected by the metabolome. In line with this it has been demonstrated that children with genetic predisposition for T1D development and that progress to T1D display an altered serum metabolic profile compared to the group of non-progressors [3,4]. The levels of succinic acid and phosphatidylcholin were reduced at birth, and elevated levels of glutamic acid preceded seroconversion, i.e. appearance of autoantibodies specific for insulin and glutamic acid decarboxylase (GAD)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
