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Review
. 2000 Aug;106(4):467-72.
doi: 10.1172/JCI10843.

Treatment of insulin resistance with peroxisome proliferator-activated receptor gamma agonists

J M Olefsky  1
Affiliations
Review

Treatment of insulin resistance with peroxisome proliferator-activated receptor gamma agonists

J M Olefsky. J Clin Invest. 2000 Aug.
No abstract available

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Figures

Figure 1
Figure 1
Schematic diagram of the mechanisms of PPARγ action. In the unliganded state (top), the PPARγ receptor exists as a heterodimer with the RXR nuclear receptor and the heterodimer is located on a PPAR response element (PPRE) of a target gene. The unliganded receptor heterodimer complex is associated with a multicomponent corepressor complex, which physically interacts with the PPARγ receptor through SMRT. The corepressor complex contains histone deacetylase (HDAC) activity, and the deacetylated state of histone inhibits transcription. After PPARγ ligand binding, the corepressor complex is dismissed and a coactivator complex is recruited to the heterodimer PPARγ receptor (bottom). The coactivator complex contains histone acetylase activity, leading to chromatin remodeling, facilitating active transcription. Adapted from Glass and Rosenfeld (29).
Figure 2
Figure 2
Selective PPAR modulator (SPPARM) model of PPARγ ligand action. Different PPARγ ligands (ligands 1, 2, and 3) bind to the ligand-binding domain of the PPARγ receptor. Each ligand receptor complex assumes a somewhat different three-dimensional conformation, leading to unique and differential interactions with cofactors, histones, other transcription factors, etc. As a result of these differential interactions, each PPARγ ligand receptor complex leads to a differential, but overlapping, pattern of gene expression. Thus, each ligand will activate, or repress, a certain set of genes, some of which are in common with other ligands, and some of which are not. Adapted from McDonnell (48).
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References

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    1. Warram JH, Martin BC, Krolewski AS, Soeldner JS, Kahn CR. Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Ann Intern Med. 1990;13:909–915. - PubMed
    1. Kruszynska Y, Yu JG, Olefsky JM, Sobel BE. Effects of troglitazone on blood concentrations of plasminogen activator inhibitor 1 in patients with type 2 diabetes and in lean and obese normal subjects. Diabetes. 2000;49:633–639. - PubMed

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