Document Type : Original Research Article
Authors
1
Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
2
Department of Biology, Payame Noor University Taft, Islamic Republic of Iran, Taft, Iran
3
Yazd Neuroendocrine Research Center, Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
Abstract
Objective: Quercetin, a natural flavonoid, offers potential benefits for ameliorating insulin resistance and may influence epigenetic mechanisms, including the expression of microRNAs (miRNAs) involved in this pathway. This study aimed to investigate the effects of quercetin on hepatic, renal, cardiac, and skeletal muscle tissues in type 2 diabetic rats by examining the expression of key miRNAs and genes involved in insulin resistance and insulin signaling pathways, as well as the correlations between their expression levels.
Materials and Methods: A diabetic model was induced in rats using high-fat diet and streptozotocin (HFD/STZ), and then, rats were treated with quercetin at a dose of 30 mg/kg/day by oral gavage for 4 weeks beginning at the time of STZ injection.
Results: RT-qPCR assays revealed that quercetin-treated HFD/STZ rats exhibited downregulation of miR-222, miR-21, miR-146a, and SOCS3 across all tissues, and miR-133a in all tissues except the liver. Conversely, there was upregulation of Akt, Glut4, and IRS1 in all tissues, miR-126 in all tissues except the liver, and PTEN in all tissues except the liver and muscle tissues. Correlation analysis revealed that the expression patterns of miRNAs show tissue-specific effects: in hepatic and renal tissues, miRNAs correlate with the decreased expression of AKT, GLUT4, and IRS1; whereas in cardiac and muscle tissues, miRNAs correlate with the decreased expression of SOCS3 and PTEN.
Conclusion:. In conclusion, our findings demonstrate that quercetin alters the expression profiles of key miRNAs and their targets, specifically through the upregulation of insulin-sensitizing genes (Akt, Glut4, and IRS1) and the downregulation of inhibitory markers (e.g., miR-21 and SOCS3), thereby modulating the molecular landscape of the insulin signaling pathway.
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