| Control of glucose homeostasis and insulin sensitivity by the Let-7 family of microRNAs. | |
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MedLine Citation:
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PMID: 22160727 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Robert J A Frost; Eric N Olson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-12-12 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 108 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-28 Completed Date: 2012-02-21 Revised Date: 2012-03-29 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 21075-80 Citation Subset: IM |
Affiliation:
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Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. robert.frost@utsouthwestern.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Blotting, Northern Blotting, Western Body Composition Body Weight Diabetes Mellitus, Type 2 / metabolism* Gene Expression Regulation / physiology Gene Knockdown Techniques Glucose / metabolism* Homeostasis / physiology* Insulin Resistance / physiology* Liver / metabolism Mice Mice, Inbred C57BL Mice, Obese Mice, Transgenic MicroRNAs / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL093039-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/MicroRNAs; 0/mirnlet7 microRNA, mouse; 50-99-7/Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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