Journal Article10.1038/NM956
Muscle-specific Pparg deletion causes insulin resistance
Andrea L. Hevener,Weimin He,Yaacov Barak,Jamie Le,Gautam Bandyopadhyay,Peter Olson,Peter Olson,Jason J. Wilkes,Ronald M. Evans,Ronald M. Evans,Jerrold M. Olefsky +10 more
TL;DR: 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 is revealed.
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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.
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Citations
PGC-1 promotes insulin resistance in liver through PPAR-α-dependent induction of TRB-3
Seung Hoi Koo,Hiroaki Satoh,Stephan Herzig,Chih-Hao Lee,Susan Hedrick,Rohit N. Kulkarni,Ronald M. Evans,Jerrold M. Olefsky,Marc Montminy +8 more
TL;DR: It is shown that, in the liver, TRB-3 is a target for PPAR-α, a fasting-inducible inhibitor of the serine-threonine kinase Akt/PKB, which indicates a link between nuclear hormone receptor and insulin signaling pathways, and suggest a potential role for TRb-3 inhibitors in the treatment of type 2 diabetes.
Biology and therapeutic applications of peroxisome proliferator- activated receptors.
TL;DR: The current and potential medical implications of PPAR ligands in various pathologies, ranging from metabolic disorders to cardiovascular disease, chronic inflammation, neurodegenerative disorders and cancer, are discussed.
Revisiting PPARγ as a target for the treatment of metabolic disorders
TL;DR: How P TM of PPARγ may be regulated and issues to be considered in making novel anti-diabetic drugs that can modulate the PTM of PParγ are discussed.
Adiponectin and PPARγ: cooperative and interdependent actions of two key regulators of metabolism.
Olga Astapova,Todd Leff +1 more
TL;DR: In this paper, the authors reviewed the interplay between peroxisome proliferator-activated receptor gamma (PPARγ) and adiponectin in regulating metabolism, presenting evidence that PPARγ regulates gene expression, processing, and secretion and that the two proteins have overlapping effects on downstream metabolic pathways.
Peroxisome Proliferator-Activated Receptor-γ Agonists Suppress Adrenocortical Tumor Cell Proliferation and Induce Differentiation
Matthias J. Betz,Igor Shapiro,Martin Fassnacht,Stefanie Hahner,Martin Reincke,Felix Beuschlein +5 more
TL;DR: Both PPARgamma-dependent and PPARGamma-independent effects of TZD treatment are likely to contribute to the observed phenotypical effects on NCI h295 cells, indicating that TZDs might have the potential to become an additional treatment option as differentiation-inducing agents in patients with ACC.
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TL;DR: It is reported that thiazolidinediones are potent and selective activators of peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily recently shown to function in adipogenesis, and raised the intriguing possibility that PPARγ is a target for the therapeutic actions of this class of compounds.
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