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dc.contributor.authorChao, Lily C.en_US
dc.contributor.authorWroblewski, Kevinen_US
dc.contributor.authorZhang, Zidongen_US
dc.contributor.authorPei, Limingen_US
dc.contributor.authorVergnes, Laurenten_US
dc.contributor.authorIlkayeva, Olga R.en_US
dc.contributor.authorDing, Shi Yingen_US
dc.contributor.authorReue, Karenen_US
dc.contributor.authorWatt, Matthew J.en_US
dc.contributor.authorNewgard, Christopher B.en_US
dc.contributor.authorPilch, Paul F.en_US
dc.contributor.authorHevener, Andrea L.en_US
dc.contributor.authorTontonoz, Peteren_US
dc.date.accessioned2011-12-29T23:32:17Z
dc.date.available2011-12-29T23:32:17Z
dc.date.issued2009-9-9
dc.identifier.citationChao, Lily C., Kevin Wroblewski, Zidong Zhang, Liming Pei, Laurent Vergnes, Olga R. Ilkayeva, Shi Ying Ding, Karen Reue, Matthew J. Watt, Christopher B. Newgard, Paul F. Pilch, Andrea L. Hevener, Peter Tontonoz. "Insulin Resistance and Altered Systemic Glucose Metabolism in Mice Lacking Nur77" Diabetes 58(12): 2788-2796. (2009)
dc.identifier.issn1939-327X
dc.identifier.urihttps://hdl.handle.net/2144/2649
dc.description.abstractOBJECTIVE: Nur77 is an orphan nuclear receptor with pleotropic functions. Previous studies have identified Nur77 as a transcriptional regulator of glucose utilization genes in skeletal muscle and gluconeogenesis in liver. However, the net functional impact of these pathways is unknown. To examine the consequence of Nur77 signaling for glucose metabolism in vivo, we challenged Nur77 null mice with high-fat feeding. RESEARCH DESIGN AND METHODS: Wild-type and Nur77 null mice were fed a high-fat diet (60% calories from fat) for 3 months. We determined glucose tolerance, tissue-specific insulin sensitivity, oxygen consumption, muscle and liver lipid content, muscle insulin signaling, and expression of glucose and lipid metabolism genes. RESULTS: Mice with genetic deletion of Nur77 exhibited increased susceptibility to diet-induced obesity and insulin resistance. Hyperinsulinemic-euglycemic clamp studies revealed greater high-fat diet–induced insulin resistance in both skeletal muscle and liver of Nur77 null mice compared with controls. Loss of Nur77 expression in skeletal muscle impaired insulin signaling and markedly reduced GLUT4 protein expression. Muscles lacking Nur77 also exhibited increased triglyceride content and accumulation of multiple even-chained acylcarnitine species. In the liver, Nur77 deletion led to hepatic steatosis and enhanced expression of lipogenic genes, likely reflecting the lipogenic effect of hyperinsulinemia. CONCLUSIONS: Collectively, these data demonstrate that loss of Nur77 influences systemic glucose metabolism and highlight the physiological contribution of muscle Nur77 to this regulatory pathway.en_US
dc.description.sponsorshipNational Institutes of Health (HD-00850, DK-081683-01, DK-30425, HL030568); American Diabetes Associationen_US
dc.language.isoen
dc.publisherAmerican Diabetes Associationen_US
dc.rights© 2009 American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.en_US
dc.titleInsulin Resistance and Altered Systemic Glucose Metabolism in Mice Lacking Nur77en_US
dc.typeArticleen_US
dc.identifier.doi10.2337/db09-0763
dc.identifier.pmid19741162
dc.identifier.pmcid2780886


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