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Cowan E, Karagiannopoulos A, Pollastri A, Asai A, Nagao M, Maziarz M, Esguerra JLS, Eliasson L
iScience 28 (12) 114200 [2025-12-19; online 2025-11-22]
Increasing evidence suggests that microRNAs (miRNAs) contribute to pancreatic β-cell compensation during type 2 diabetes (T2D) pathogenesis. To examine miRNA-mRNA interactions in human islets and their roles in β-cell insulin secretion and T2D, we performed small-RNA sequencing on pancreatic islets from nine individuals with T2D and 52 non-diabetic controls. We identified 70 differentially expressed miRNAs, with miRNAs upregulated in T2D enriched in a co-expression network associated with insulin secretion. Eight such upregulated miRNAs, including miR-101-3p and miR-9-5p associated with both first- and second-phase insulin secretion. Among them, miR-101-3p had the most mRNA targets, while highly abundant mRNA transcripts (e.g., INS) were regulated by few miRNAs. Overexpression of miR-101-3p in β-cells increased insulin release in vitro and reduced expression of CADM1, a target of miR-101-3p. In summary, we have comprehensively identified miRNA-mRNA alterations in human islets associated with T2D pathogenesis and propose that miR-101-3p plays an important role in β-cell insulin secretion.
PubMed 41438030
DOI 10.1016/j.isci.2025.114200
Crossref 10.1016/j.isci.2025.114200
pmc: PMC12721147
pii: S2589-0042(25)02461-7