Altered metabolic signature in pre-diabetic NOD mice.

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 wa...

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Main Authors: Rasmus Madsen, Viqar Showkat Banday, Thomas Moritz, Johan Trygg, Kristina Lejon
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22514744/?tool=EBI
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author Rasmus Madsen
Viqar Showkat Banday
Thomas Moritz
Johan Trygg
Kristina Lejon
author_facet Rasmus Madsen
Viqar Showkat Banday
Thomas Moritz
Johan Trygg
Kristina Lejon
author_sort Rasmus Madsen
collection DOAJ
description 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.
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spelling doaj.art-32720852024041d8997e596e9ae427722022-12-21T18:33:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3544510.1371/journal.pone.0035445Altered metabolic signature in pre-diabetic NOD mice.Rasmus MadsenViqar Showkat BandayThomas MoritzJohan TryggKristina LejonAltered 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22514744/?tool=EBI
spellingShingle Rasmus Madsen
Viqar Showkat Banday
Thomas Moritz
Johan Trygg
Kristina Lejon
Altered metabolic signature in pre-diabetic NOD mice.
PLoS ONE
title Altered metabolic signature in pre-diabetic NOD mice.
title_full Altered metabolic signature in pre-diabetic NOD mice.
title_fullStr Altered metabolic signature in pre-diabetic NOD mice.
title_full_unstemmed Altered metabolic signature in pre-diabetic NOD mice.
title_short Altered metabolic signature in pre-diabetic NOD mice.
title_sort altered metabolic signature in pre diabetic nod mice
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22514744/?tool=EBI
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AT thomasmoritz alteredmetabolicsignatureinprediabeticnodmice
AT johantrygg alteredmetabolicsignatureinprediabeticnodmice
AT kristinalejon alteredmetabolicsignatureinprediabeticnodmice