Cited by 280Pancreatic function and diabetesMicroRNA in disease regulationDiabetes and associated disorders

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miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors

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Melkman‐Zehavi, Tal, Oren, Roni, Kredo‐Russo, Sharon, Shapira, Tirosh, Mandelbaum, Amitai D, Rivkin, Natalia, Nir, Tomer, Lennox, Kim A, Behlke, Mark A, Dor, Yuval, Hornstein, Eran·2011·The EMBO Journal

DOI 10.1038/emboj.2010.361PMC PMC3049206

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Abstract

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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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
ORCID: Oren, Roni
Shapira, Tirosh
Mandelbaum, Amitai D
Nir, Tomer
Behlke, Mark A
Dor, Yuval
Hornstein, Eran
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 2011-02-01
Volume: 30
Issue: 5
Pages: 835-845
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1038/emboj.2010.361
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: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
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 › Endocrinology, Diabetes and Metabolism › 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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miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors

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