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Type 1 diabetes mellitus (T1DM) results from progressive damage to pancreatic β- cells, leading to insufficient insulin production and impaired glucose regulation. The autoimmune destruction of β-cells reduces their functional mass, causing chronic hyperglycemia and associated complications. Recently, microRNAs (miRNAs) have emerged as important regulators of gene expression and play key roles in various cellular processes and pathways. This review aims to provide a comprehensive overview of how miRNA-375 influences β-cell biology and to explore its potential as a therapeutic target in T1DM. By examining the complex interplay between miRNA-375, β-cell function, and autoimmunity, this article contributes to the development of strategies for early detection, prevention, and potential treatment of T1DM. Electronic databases, including PubMed/Medline, Scopus, and Google Scholar, were searched for case reports and series, case-control, cohort, and cross-sectional studies, as well as reviews, from the inception of the databases to December 2024. The role of miRNAs in the onset and progression of T1DM has received considerable attention in recent years. Among them, miRNA- 375 is particularly significant due to its influence on β-cell function and apoptosis. Alterations in miRNA-375 levels have been observed during both the preclinical and clinical stages of T1DM. Developing reliable, non-invasive methods for monitoring miRNA-375 is critical for translating these findings into clinical applications. Future research should focus on establishing highly sensitive and specific assays for its measurement.