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Network-based insights into miRNA regulation of D-cell insulin secretion in type 2 diabetes.
iScience 28:114200 (2025)
Increasing evidence suggests that microRNAs (miRNAs) contribute to pancreatic D-cell compensation during type 2 diabetes (T2D) pathogenesis. To examine miRNA-mRNA interactions in human islets and their roles in D-cell insulin secretion and T2D, we performed small-RNA sequencing on pancreatic islets from nine individ-uals 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 upre-gulated 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 D-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 D-cell insulin secretion.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Pancreatic-islets; Expression; Exocytosis; Micrornas; Genes; Identification; Transcriptome; Dysfunction; Individuals; Mir-375
ISSN (print) / ISBN
2589-0042
e-ISSN
2589-0042
Journal
iScience
Quellenangaben
Volume: 28,
Issue: 12,
Article Number: 114200
Publisher
Elsevier
Publishing Place
Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Reviewing status
Peer reviewed
Institute(s)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants
Royal Physiographic society in Lund
Region Skane-ALF
Region Skane-ALF