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Cowan, E.* ; Karagiannopoulos, A.* ; Pollastri, A. ; Asai, A.* ; Nagao, M.* ; Maziarz, M.* ; Esguerra, J.L.S.* ; Eliasson, L.*

Network-based insights into miRNA regulation of D-cell insulin secretion in type 2 diabetes.

iScience 28:114200 (2025)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Pancreatic-islets; Expression; Exocytosis; Micrornas; Genes; Identification; Transcriptome; Dysfunction; Individuals; Mir-375
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Zeitschrift iScience
Quellenangaben Band: 28, Heft: 12, Seiten: , Artikelnummer: 114200 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Förderungen Royal Physiographic society in Lund
Region Skane-ALF