DYSREGULATION OF CIRCULATING miRNAs IN HIGH-FAT DIET AND STREPTOZOTOCIN-INDUCED TYPE 2 DIABETES MELLITUS IN WISTAR ALBINO RATS

Background: Endothelial dysfunction is a major contributor to the vascular complications of type 2 diabetes mellitus. Circulating microRNAs (miRNAs) have emerged as promising biomarkers and potential modulators of metabolic and cardiovascular diseases. This study aimed to investigate the expression profiles of selected circulating miRNAs in a rat model of T2DM induced by a high-fat diet (HFD) and low-dose streptozotocin (STZ). Methods: Male Wistar albino rats were divided into four groups and subjected to dietary and chemical interventions to induce T2DM. Serum and circulating miRNAs were isolated and quantified using real-time quantitative reverse transcription PCR (qRT-PCR). The expression levels of miR-126, miR-30a-5p were analyzed across control and diabetic groups, with U6 small nuclear RNA as an internal control. Results: The diabetic groups exhibited significant downregulation of miR-126, suggesting its protective role in vascular integrity and metabolic regulation. In contrast, miR-30a-5p was markedly upregulated in response to High-Fat Diet + STZ (HFD+STZ) induced metabolic stress, implicating it in diabetes-associated metabolic disturbances. Notably, combined HFD and STZ exposure further amplified these alterations in miRNA expression. Conclusion: Our findings reveal distinct alterations in circulating miRNA expression associated with T2DM and its vascular complications. Specifically, reduced miR-126 expression and increased miR-30a-5p expression may contribute to endothelial dysfunction and metabolic dysregulation. These miRNAs may serve as potential non-invasive biomarkers for early diagnosis and disease monitoring in T2DM. Further clinical validation and mechanistic studies are warranted.