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Control of glucose homeostasis and insulin sensitivity by the Let-7 family of microRNAs
Open accessAbstract
Diabetes mellitus is the most common metabolic disorder worldwide and a major risk factor for cardiovascular disease. MicroRNAs are negative regulators of gene expression that have been implicated in many biological processes, including metabolism. Here we show that the Let-7 family of microRNAs regulates glucose metabolism in multiple organs. Global and pancreas-specific overexpression of Let-7 in mice resulted in impaired glucose tolerance and reduced glucose-induced pancreatic insulin secretion. Mice overexpressing Let-7 also had decreased fat mass and body weight, as well as reduced body size. Global knockdown of the Let-7 family with an antimiR was sufficient to prevent and treat impaired glucose tolerance in mice with diet-induced obesity, at least in part by improving insulin sensitivity in liver and muscle. AntimiR treatment of mice on a high-fat diet also resulted in increased lean and muscle mass, but not increased fat mass, and prevented ectopic fat deposition in the liver. These findings demonstrate that Let-7 regulates multiple aspects of glucose metabolism and suggest antimiR-induced Let-7 knockdown as a potential treatment for type 2 diabetes mellitus. Furthermore, our Cre -inducible Let-7 -transgenic mice provide a unique model for studying tissue-specific aspects of body growth and type 2 diabetes.
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Krek, A., Grün, D., Poy, M. N., Wolf, R., Rosenberg, L., Epstein, E. J., MacMenamin, P., da Piedade, I., Gunsalus, K. C., Stoffel, M., et al. (2005) · Nature Genetics · doi:10.1038/ng1536 · Cited by 4,603
A pancreatic islet-specific microRNA regulates insulin secretion
Poy, M. N., Eliasson, L., Krutzfeldt, J., Kuwajima, S., Ma, X., MacDonald, P. E., Pfeffer, S., Tuschl, T., Rajewsky, N., Rorsman, P., et al. (2004) · Nature · doi:10.1038/nature03076 · Cited by 2,102
MicroRNAs 103 and 107 regulate insulin sensitivity
Trajkovski, M., Hausser, J., Soutschek, J., Bhat, B., Akin, A., Zavolan, M., Heim, M. H., & Stoffel, M. (2011) · Nature · doi:10.1038/nature10112 · Cited by 1,000
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McCarthy, M. I. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0906948 · Cited by 938
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Metadata
- Authors
- Frost, R. J. A., & Olson, E. N.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2011-12-12
- Volume
- 108
- Issue
- 52
- Pages
- 21075-21080
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1976840283
- Cited by
- 446
- References
- 5
- FWCI
- 10.50
- Type
- journal article
- Language
- en
- Open access
- green
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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