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Metabolomics and Lipidomics Study of Mouse Models of Type 1 Diabetes Highlights Divergent Metabolism in Purine and Tryptophan Metabolism Prior to Disease Onset.
- Source :
-
Journal of proteome research [J Proteome Res] 2018 Mar 02; Vol. 17 (3), pp. 946-960. Date of Electronic Publication: 2018 Feb 12. - Publication Year :
- 2018
-
Abstract
- With the increase in incidence of type 1 diabetes (T1DM), there is an urgent need to understand the early molecular and metabolic alterations that accompany the autoimmune disease. This is not least because in murine models early intervention can prevent the development of disease. We have applied a liquid chromatography (LC-) and gas chromatography (GC-) mass spectrometry (MS) metabolomics and lipidomics analysis of blood plasma and pancreas tissue to follow the progression of disease in three models related to autoimmune diabetes: the nonobese diabetic (NOD) mouse, susceptible to the development of autoimmune diabetes, and the NOD-E (transgenic NOD mice that express the I-E heterodimer of the major histocompatibility complex II) and NOD-severe combined immunodeficiency (SCID) mouse strains, two models protected from the development of diabetes. All three analyses highlighted the metabolic differences between the NOD-SCID mouse and the other two strains, regardless of diabetic status indicating that NOD-SCID mice are poor controls for metabolic changes in NOD mice. By comparing NOD and NOD-E mice, we show the development of T1DM in NOD mice is associated with changes in lipid, purine, and tryptophan metabolism, including an increase in kynurenic acid and a decrease in lysophospholipids, metabolites previously associated with inflammation.
- Subjects :
- Animals
Autoimmunity
Chromatography, Liquid
Diabetes Mellitus, Type 1 immunology
Diabetes Mellitus, Type 1 pathology
Discriminant Analysis
Disease Models, Animal
Female
Gas Chromatography-Mass Spectrometry
Gene Expression
Histocompatibility Antigens Class II genetics
Histocompatibility Antigens Class II immunology
Islets of Langerhans immunology
Islets of Langerhans pathology
Kynurenic Acid metabolism
Lysophospholipids metabolism
Metabolomics methods
Mice
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
Prediabetic State immunology
Prediabetic State pathology
Principal Component Analysis
Protein Multimerization
Diabetes Mellitus, Type 1 metabolism
Islets of Langerhans metabolism
Lipid Metabolism
Prediabetic State metabolism
Purines metabolism
Tryptophan metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1535-3907
- Volume :
- 17
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of proteome research
- Publication Type :
- Academic Journal
- Accession number :
- 28994599
- Full Text :
- https://doi.org/10.1021/acs.jproteome.7b00489