miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors
Open accessAbstract
MicroRNAs (miRNAs) were shown to be important for pancreas development, yet their roles in differentiated β-cells remain unclear. Here, we show that miRNA inactivation in β-cells of adult mice results in a striking diabetic phenotype. While islet architecture is intact and differentiation markers are maintained, Dicer1-deficient β-cells show a dramatic decrease in insulin content and insulin mRNA. As a consequence of the change in insulin content, the animals become diabetic. We provide evidence for involvement of a set of miRNAs in regulating insulin synthesis. The specific knockdown of miR-24, miR-26, miR-182 or miR-148 in cultured β-cells or in isolated primary islets downregulates insulin promoter activity and insulin mRNA levels. Further, miRNA-dependent regulation of insulin expression is associated with upregulation of transcriptional repressors, including Bhlhe22 and Sox6. Thus, miRNAs in the adult pancreas act in a new network that reinforces insulin expression by reducing the expression of insulin transcriptional repressors.
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A variety of microRNAs influence pancreatic beta cell development and function.
“a variety of microRNAs have been shown to influence pancreatic beta cell development and function.”
From The Vasculature in Prediabetes (2018) · cites this paper as [137]
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Self-citation
- Authors
- Melkman‐Zehavi, T., Oren, R., Kredo‐Russo, S., Shapira, T., Mandelbaum, A. D., Rivkin, N., Nir, T., Lennox, K. A., Behlke, M. A., Dor, Y., & Hornstein, E.
- Affiliations
- Weizmann Institute of Science (IL)
- Hebrew University of Jerusalem (IL)
- Integrated DNA Technologies (United States) (US)
- Corresponding author
- Hornstein, Eran
- Venue
- The EMBO Journal
- Published
- 2011-02-01
- Volume
- 30
- Issue
- 5
- Pages
- 835-845
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC3049206
- OpenAlex
- W2101072639
- Cited by
- 280
- References
- 46
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 10 · 2023: 9 · 2022: 17 · 2021: 21 · 2020: 23 · 2019: 18 · 2018: 16 · 2017: 23 · 2016: 16 · 2015: 34 · 2014: 27 · 2013: 26 · 2012: 18
- FWCI
- 26.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- European Commission (241883)
- European Foundation for the Study of Diabetes
- Israel Science Foundation (99-2007-71)
- Wolfson Family Charitable Trust (99-2007-71)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- microRNA, pancreatic beta cells, insulin gene expression, DICER1, diabetes mellitus, transcriptional repressor, SOX6, miR-24, miR-26, miR-182, miR-148, islets
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Endoribonucleases, Humans, Immunoenzyme Techniques, Insulin, Luciferases, Repressor Proteins, RNA, Messenger, Transcription, Genetic, Blotting, Western, Down-Regulation, Glucose Intolerance, Mice, Knockout, Integrases, Reverse Transcriptase Polymerase Chain Reaction, MicroRNAs, Ribonuclease III, Insulin-Secreting Cells, Mice, DEAD-box RNA Helicases
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