First Author | Hevener AL | Year | 2003 |
Journal | Nat Med | Volume | 9 |
Issue | 12 | Pages | 1491-7 |
PubMed ID | 14625542 | Mgi Jnum | J:86773 |
Mgi Id | MGI:2682080 | Doi | 10.1038/nm956 |
Citation | Hevener AL, et al. (2003) Muscle-specific Pparg deletion causes insulin resistance. Nat Med 9(12):1491-7 |
abstractText | Thiazolidinediones (TZDs) are insulin-sensitizing drugs and are potent agonists of the nuclear peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Although muscle is the major organ responsible for insulin-stimulated glucose disposal, PPAR-gamma 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-gamma, in mouse skeletal muscle. As early as 4 months of age, mice with targeted disruption of PPAR-gamma 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 approximately 80% and was unchanged by 3 weeks of TZD treatment. These effects reveal a crucial role for muscle PPAR-gamma in the maintenance of skeletal muscle insulin action, the etiology of insulin resistance and the action of TZDs. |