Muscle-specific Pparg deletion causes insulin resistance
Author: ["Andrea L Hevener","Weimin He","Yaacov Barak","Jamie Le","Gautam Bandyopadhyay","Peter Olson","Jason Wilkes","Ronald M Evans","Jerrold Olefsky"]
Publication: Nature Medicine
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Abstract
Thiazolidinediones (TZDs) are insulin-sensitizing drugs and are potent agonists of the nuclear peroxisome proliferator-activated receptor-γ (PPAR-γ). Although muscle is the major organ responsible for insulin-stimulated glucose disposal, PPAR-γ 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-γ, in mouse skeletal muscle. As early as 4 months of age, mice with targeted disruption of PPAR-γ 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-γ in the maintenance of skeletal muscle insulin action, the etiology of insulin resistance and the action of TZDs.
Cite this article
Hevener, A., He, W., Barak, Y. et al. Muscle-specific Pparg deletion causes insulin resistance. Nat Med 9, 1491–1497 (2003). https://doi.org/10.1038/nm956
