Elucidating the Role of MicroRNAs in Regulating Insulin Signaling Pathways: Implications for the Pathophysiology and Treatment of Type 2 Diabetes
Khan, Imran Saeed, Muhammad Hamza Amjad, Ammarah Khan, Faiza Khan, Qudsia Umaira Raja, Sohail Khan Khan, Rida
Khan, Imran
Saeed, Muhammad Hamza
Amjad, Ammarah
Khan, Faiza
Khan, Qudsia Umaira
Raja, Sohail Khan
Khan, Rida
Affiliation
The Dudley Group NHS Foundation Trust
Other Contributors
Publication date
2025-07-10
Subject
Collections
Research Projects
Organizational Units
Journal Issue
Abstract
Background This retrospective cross-sectional analysis assessed the regulatory role of microRNA-375 (miR-375) in the insulin signaling pathway and its clinical relevance for the treatment of type 2 diabetes mellitus (T2DM) in a Pakistani cohort. Methodology The study analyzed data from 300 adult patients with clinically confirmed T2DM to identify associations between miR-375 expression levels, insulin signaling pathway-specific biomarkers, glycemic indices, and treatment response. Results The mean miR-375 levels were found to be inversely correlated with HbA1c (r = -0.31, p < 0.01) and positively correlated with both insulin receptor substrate 1 expression (r = 0.29, p < 0.01) and phosphoinositide 3-kinase activity (r = 0.25, p < 0.01), indicating a proportionately enhanced insulin sensitivity with increased miR-375 expression. The one-way analysis of variance revealed significant differences in the expression of glucose transporter type 4 (GLUT4) between the three therapy response groups, with improved therapy responders displaying higher GLUT4 levels (p = 0.012). Logistic regression models identified miR-375 (odds ratio (OR) = 0.71, p < 0.05) and Framingham Risk Score (OR = 1.46, p < 0.001) as microRNA and clinical predictors, respectively, for cardiovascular disease, indicating its promise as a potential predictive biomarker. Hierarchical k-means clustering identified distinct patient subtypes to identify a high-risk patient profile based on insulin signaling and treatment adherence behaviors. Cluster 1, with high miR-375 and insulin sensitivity indicators, was associated with superior glycemic management and fewer comorbidities among participants in the study. Conclusions The results support the incorporation of miR-375 profiling in clinical practice to improve therapeutic stratification for T2DM by providing successful treatment predictions to improve metabolic outcomes. This study builds upon earlier findings and initiates a deeper understanding of miRNA-mediated modulation of the pathophysiology associated with T2DM. miR-375 is highlighted as a candidate biomarker for precision medicine.
Citation
Khan I, Saeed MH, Amjad A, Khan F, Khan QU, Raja SK, Khan R. Elucidating the Role of MicroRNAs in Regulating Insulin Signaling Pathways: Implications for the Pathophysiology and Treatment of Type 2 Diabetes. Cureus. 2025 Jul 10;17(7):e87682. doi: 10.7759/cureus.87682
Type
Article