Pathogenesis of impaired glucose tolerance in rats based on transcriptome analysis

基于转录组分析的大鼠葡萄糖耐量受损的发病机制

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Abstract

Impaired glucose tolerance (IGT) is a transitional stage in the development of Type 2 diabetes mellitus (T2DM), but understanding its pathogenesis is currently insufficient. This study established the IGT rats through a high-fat diet combined with intraperitoneal Streptozotocin (STZ) injection to investigate the pathogenesis via transcriptomic profiling of liver tissues. Through transcriptome analysis, a total of 860 up-regulated and 707 down-regulated differentially expressed genes (DEGs) were identified. Enrichment analysis highlighted the PPAR signaling pathway as central to the pathology of IGT. Protein-protein interaction (PPI) network analysis identified IL-1b, Stat1, Igf-1, and Cyp7a1 as Target DEGs (T-DEGs), which were validated by Western blot analysis. Elevated serum levels of IL-6, IFNγ, TNFα, and IL-1β were confirmed via ELISA analysis. The results suggested that signaling pathways such as STAT1/PPARγ/IGF-1, STAT1/PPARγ/Cyp7a1, and STAT1/PPARγ/IL-1β may play crucial roles in the pathogenesis of IGT. These findings provide insight into potential mechanisms and targets for early diagnosis and therapeutic intervention.

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