AI Article Synopsis
- The study aims to explore how the metabolite composition of rat supraspinatus tendons changes at different stages of diabetes using untargeted metabolomics analysis.
- 80 Sprague-Dawley rats were divided into a normal group and a type 2 diabetes group, with diabetic rats further categorized based on the duration of their diabetes (4, 12, and 24 weeks), allowing for comparison of metabolite profiles.
- Results identified 94, 36, and 86 differentially expressed metabolites (DEMs) in the tendons at various stages, with seven key metabolites linked to sustained changes identified as biomarkers, particularly highlighting the impact of diabetes on purine metabolism.
Article Abstract
Objective: To investigate the dynamic changes of metabolite composition in rat supraspinatus tendons at different stages of diabetes by untargeted metabolomics analysis.
Methods: A total of 80 Sprague-Dawley rats were randomly divided into normal (NG, n = 20) and type 2 diabetes mellitus groups (T2DM, n = 60) and subdivided into three groups according to the duration of diabetes: T2DM-4w, T2DM-12w, and T2DM-24w groups; the duration was calculated from the time point of T2DM rat model establishment. The three comparison groups were set up in this study, T2DM-4w group . NG, T2DM-12w group . T2DM-4w group, and T2DM-24w group . T2DM-12w group. The metabolite profiles of supraspinatus tendon were obtained using tandem mass spectrometry. Metabolomics multivariate statistics were used for metabolic data analysis and differential metabolite (DEM) determination. The intersection of the three comparison groups' DEMs was defined as key metabolites that changed consistently in the supraspinatus tendon after diabetes induction; then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed.
Results: T2DM-4w group vs. NG, T2DM-12w group vs. T2DM-4w group, and T2DM-24w group vs. T2DM-12w group detected 94 (86 up-regulated and 8 down-regulated), 36 (13 up-regulated and 23 down-regulated) and 86 (24 up-regulated and 62 down-regulated) DEMs, respectively. Seven key metabolites of sustained changes in the supraspinatus tendon following induction of diabetes include D-Lactic acid, xanthine, O-acetyl-L-carnitine, isoleucylproline, propoxycarbazone, uric acid, and cytidine, which are the first identified biomarkers of the supraspinatus tendon as it progresses through the course of diabetes. The results of KEGG pathway enrichment analysis showed that the main pathway of supraspinatus metabolism affected by diabetes (p < 0.05) was purine metabolism. The results of the KEGG metabolic pathway . DEMs correlation network graph revealed that uric acid and xanthine play a role in more metabolic pathways.
Conclusion: Untargeted metabolomics revealed the dynamic changes of metabolite composition in rat supraspinatus tendons at different stages of diabetes, and the newly discovered seven metabolites, especially uric acid and xanthine, may provide novel research to elucidate the mechanism of diabetes-induced tendinopathy.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694349 | PMC |
| http://dx.doi.org/10.3389/fendo.2023.1292103 | DOI Listing |
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