Muscle-specific Pparg deletion causes insulin resistance.
Document Type
Article
Publication Date
2003
Keywords
Animals, Gene-Expression, Glucose-Clamp-Technique, Insulin, Insulin-Resistance, Liver, Mice-Inbred-C57BL, Mice-Knockout, Mice-Transgenic, Monosaccharide-Transport-Proteins, Muscle-Skeletal, RNA-Messenger, Receptors-Cytoplasmic-and-Nuclear, Signal-Transduction, Thiazolidinediones, Transcription-Factors
First Page
1491
Last Page
1497
JAX Source
Nat Med 2003 Dec; 9(12):1491-7.
Abstract
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.
Recommended Citation
Hevener AL,
He W,
Barak Y,
Le J,
Bandyopadhyay G,
Olson P,
Wilkes J,
Evans RM,
Olefsky J.
Muscle-specific Pparg deletion causes insulin resistance. Nat Med 2003 Dec; 9(12):1491-7.