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

Cowan, Elaine LU orcid ; Karagiannopoulos, Alexandros LU orcid ; Pollastri, Alessio LU ; Asai, Akira LU ; Nagao, Mototsugu LU ; Maziarz, Marlena LU orcid ; Esguerra, Jonathan L.S. LU orcid and Eliasson, Lena LU orcid (2025) In iScience 28(12). p.1-13
Abstract

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)... (More)

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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biological sciences, cell biology, health sciences, molecular mechanism of gene regulation
in
iScience
volume
28
issue
12
article number
114200
pages
1 - 13
publisher
Elsevier
external identifiers
  • scopus:105024009739
ISSN
2589-0042
DOI
10.1016/j.isci.2025.114200
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s)
id
066fb5a1-f75b-4d24-8967-d126c3a9aca6
date added to LUP
2025-12-14 19:01:51
date last changed
2025-12-15 07:32:20
@article{066fb5a1-f75b-4d24-8967-d126c3a9aca6,
  abstract     = {{<p>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.</p>}},
  author       = {{Cowan, Elaine and Karagiannopoulos, Alexandros and Pollastri, Alessio and Asai, Akira and Nagao, Mototsugu and Maziarz, Marlena and Esguerra, Jonathan L.S. and Eliasson, Lena}},
  issn         = {{2589-0042}},
  keywords     = {{biological sciences; cell biology; health sciences; molecular mechanism of gene regulation}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{12}},
  pages        = {{1--13}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{Network-based insights into miRNA regulation of β-cell insulin secretion in type 2 diabetes}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2025.114200}},
  doi          = {{10.1016/j.isci.2025.114200}},
  volume       = {{28}},
  year         = {{2025}},
}