MicroRNAs (miRNAs) are small RNAs that posttranscriptionally repress gene expression of their target mRNAs. miRNA discovery dates to 1993, when Ambros and Ruvkun identified them in nematodes. More than two decades later, their pioneering research was recognized with the Nobel Prize in Medicine, a fitting acknowledgment of the profound impact these tiny molecules exert on nearly every biological process and disease studied to date. The regulation of pancreatic islet function, critical for glucose homeostasis and diabetes development, is no exception. The identification of miR-375 as a key regulator of insulin secretion in 2004 provided the first connection between miRNAs and islets, followed by studies showing that miRNAs are essential for endocrine development. Research in this field has since expanded rapidly, yielding insights into how miRNAs influence nutrient sensing, glucose metabolism, and diabetes pathogenesis while also highlighting their potential as biomarkers and therapeutic targets. Despite this progress, the field still faces major challenges. The mechanisms controlling miRNA expression, their precise roles in islet function and diabetes progression, and strategies for their therapeutic modulation remain poorly defined. In this perspective, we summarize key findings in islet miRNA biology and diabetes and critically discuss knowledge gaps, technical challenges, and translational opportunities that define this rapidly evolving field.
- This perspective marks the commemoration of the 2024 Nobel Prize in Medicine for miRNA discovery and reflects on more than two decades of research linking MicroRNAs (miRNAs) to islet biology and diabetes.
- We very briefly summarize key roles of islet miRNAs in β-cell development, function, and immune interactions and identify major gaps in current knowledge.
- We discuss emerging concepts in miRNA regulation, cellular heterogeneity, and therapeutic targeting, alongside ongoing challenges in biomarker validation.
- Our view underscores that integrating mechanistic, single-cell, and translational approaches will be essential to advance miRNA-based therapies.
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