Muscle-specific Pparg deletion causes insulin resistance.
In: Nature Medicine, Jg. 9 (2003-12-01), Heft 12, S. 1491-1497
academicJournal
Zugriff:
Thiazolidinediones (TZDs) are insulin-sensitizing drugs and are potent agonists of the nuclear peroxisome proliferator-activated receptor-? (PPAR-?). Although muscle is the major organ responsible for insulin-stimulated glucose disposal, PPAR-? is more highly expressed in adipose tissue than in muscle. To address this issue, we used the Cre-loxP system to knock out Pparg, the gene encoding PPAR-?, in mouse skeletal muscle. As early as 4 months of age, mice with targeted disruption of PPAR-? in muscle showed glucose intolerance and progressive insulin resistance. Using the hyperinsulinemic-euglycemic clamp technique, the in vivo insulin-stimulated glucose disposal rate (IS-GDR) was reduced by ~80% and was unchanged by 3 weeks of TZD treatment. These effects reveal a crucial role for muscle PPAR-? in the maintenance of skeletal muscle insulin action, the etiology of insulin resistance and the action of TZDs. [ABSTRACT FROM AUTHOR]
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Muscle-specific Pparg deletion causes insulin resistance.
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Autor/in / Beteiligte Person: | Hevener, Andrea L. ; He, Weimin ; Barak, Yaacov ; Le, Jamie ; Bandyopadhyay, Gautam ; Olson, Peter ; Wilkes, Jason ; Evans, Ronald M. ; Olefsky, Jerrold |
Zeitschrift: | Nature Medicine, Jg. 9 (2003-12-01), Heft 12, S. 1491-1497 |
Veröffentlichung: | 2003 |
Medientyp: | academicJournal |
ISSN: | 1078-8956 (print) |
DOI: | 10.1038/nm956 |
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