Murfitt, SA, Zaccone, P, Wang, X et al. (6 more authors) (2018) A metabolomics and lipidomics study of mouse models of type 1 diabetes highlights divergent metabolism in purine and tryptophan metabolism prior to disease on-set. Journal of Proteome Research, 17 (3). pp. 946-960. ISSN 1535-3893
Abstract
With the increase in incidence of type 1 diabetes (T1DM), particularly in Westernised societies, 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 overt disease. In this study we have applied a liquid chromatography (LC-) and gas chromatography (GC-) mass spectrometry (MS) metabolomics and lipidomics analysis of blood plasma and pancreas tissue extracts to follow the progression of disease in three models related to autoimmune diabetes: the non-obese diabetic (NOD) mouse, which is 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. Comparing between the NOD and NOD-E mice we show the development of T1DM in the NOD mouse 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017, American Chemical Society. This document is the Accepted Manuscript version of a Published Work that will appear in final form in Journal of Proteome Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.jproteome.7b00489. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Non Obese Diabetic (NOD) mouse, NOD-severe combined immunodeficiency (SCID) mouse, mass spectrometry, xanthinine, kynurenic acid. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 13 Oct 2017 09:47 |
Last Modified: | 10 Oct 2018 00:38 |
Status: | Published |
Publisher: | American Chemical Society |
Identification Number: | 10.1021/acs.jproteome.7b00489 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:122412 |