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MicroRNAs 103 and 107 regulate insulin sensitivity
Open accessAbstract
Defects in insulin signalling are among the most common and earliest defects that predispose an individual to the development of type 2 diabetes. MicroRNAs have been identified as a new class of regulatory molecules that influence many biological functions, including metabolism. However, the direct regulation of insulin sensitivity by microRNAs in vivo has not been demonstrated. Here we show that the expression of microRNAs 103 and 107 (miR-103/107) is upregulated in obese mice. Silencing of miR-103/107 leads to improved glucose homeostasis and insulin sensitivity. In contrast, gain of miR-103/107 function in either liver or fat is sufficient to induce impaired glucose homeostasis. We identify caveolin-1, a critical regulator of the insulin receptor, as a direct target gene of miR-103/107. We demonstrate that caveolin-1 is upregulated upon miR-103/107 inactivation in adipocytes and that this is concomitant with stabilization of the insulin receptor, enhanced insulin signalling, decreased adipocyte size and enhanced insulin-stimulated glucose uptake. These findings demonstrate the central importance of miR-103/107 to insulin sensitivity and identify a new target for the treatment of type 2 diabetes and obesity.
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“MicroRNA inhibitors (antagomirs) targeting miR-103 and miR-107 improve insulin sensitivity and reduce adiposity in diet-induced obese mice by enhancing hepatic and peripheral insulin signaling [92].”
From Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies (2025) · cites this paper as [92]
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Metadata
- Authors
- Trajkovski, M., Hausser, J., Soutschek, J., Bhat, B., Akin, A., Zavolan, M., Heim, M. H., & Stoffel, M.
- Affiliations
- ETH Zurich (CH)
- University of Basel (CH)
- Regulus Therapeutics (United States) (US)
- University Hospital of Basel (CH)
- Corresponding author
- Stoffel, Markus
- Venue
- Nature
- Published
- 2011-06
- Volume
- 474
- Issue
- 7353
- Pages
- 649-653
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2075317528
- Cited by
- 1,000
- References
- 27
- Citations by year
- 2026: 36 · 2025: 34 · 2024: 54 · 2023: 45 · 2022: 61 · 2021: 61 · 2020: 71 · 2019: 68 · 2018: 80 · 2017: 65 · 2016: 98 · 2015: 90 · 2014: 90 · 2013: 77 · 2012: 57
- FWCI
- 25.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- BIROn (Birkbeck, University of London) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Juvenile Diabetes Research Foundation International
- Fondation Leducq
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- microRNA-107, insulin sensitivity, caveolin-1, insulin signaling, insulin receptor, glucose homeostasis, obesity, type 2 diabetes, adipocytes, liver, insulin-stimulated glucose uptake, adipocyte size, miRNA target genes
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Disease Models, Animal, Gene Expression Regulation, Glucose, Homeostasis, Hyperglycemia, Insulin, Liver, Male, Mice, Inbred C57BL, Signal Transduction, Up-Regulation, Gene Expression, Adipocytes, Gene Silencing, MicroRNAs, Cell Size, Caveolin 1, Mice
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