Cited by 1,000MicroRNA in disease regulationMetabolism, Diabetes, and CancerAdipokines, Inflammation, and Metabolic Diseases

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MicroRNAs 103 and 107 regulate insulin sensitivity

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Trajkovski, Mirko, Hausser, Jean, Soutschek, Jürgen, Bhat, Bal, Akin, Akinc, Zavolan, Mihaela, Heim, Markus H., Stoffel, Markus·2011·Nature

DOI 10.1038/nature10112

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Abstract

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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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
ORCID: Trajkovski, Mirko
Hausser, Jean
Zavolan, Mihaela
Heim, Markus H.
Stoffel, Markus
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2011-06
Volume: 474
Issue: 7353
Pages: 649-653
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature10112
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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