Peroxisome proliferator-activated receptor PPARy

Thiazolidinediones (synonyms glitazones, insulin sensitizers rosiglitazone, pioglitazone) are a novel class of oral antidiabetic drugs that activate the transcription factor peroxisome proliferator-activated receptor (PPARy). Thiazolidinediones ameliorate insulin resistance in obese animal models and in individuals... 

Receptor peroxisome proliferator-activated receptor (PPARy, human)... 

Thiazolidinediones (PPARy-agonists) Thiazolidine-diones ( pioglitazone, rosiglitazone) lower blood glucose levels in animal models of insulin resistance and also in insulin resistant patients. They are agonists of the peroxisome proliferator-activated receptor y (PPARy). Because they enhance the effect of insulin and reduce serum insulin levels in insulin resistant patients, thiazolidinediones are usually referred to as insulin sensitizers . 

Finally, it has to be mentioned that LPA also has an intracellular target site, which is the nuclear transcription factor, peroxisome proliferator-activated receptor-y (PPARy). LPA competes for thiazolidinedione binding and activates PPARy-dependent gene transcription. Thereby, LPA induced neointima formation in a rat carotid artery model. 

Peroxisome Proliferator-Activated Receptors. Table 2 PPARy target tissues, cellular effects, and physiological effects... 

TF transcription factor, R receptor, Fur ferric uptake regulation protein, NF-kB nuclear factor-kB, AP-1 activator protein-1, Egr-1 early growth response-1, VDR la,25-dihydroxy-vitamin D3 receptor, RXR retinoid X receptor, PPARy peroxisome proliferator-activated receptor y NFAT nuclear factor of activated T-cells, HSF heat shock factor, p53 tumor suppressor p53, HIF-1 hypoxia inducible factor-1. ... 

Han, K. L., Jung, M. H., Sohn, J. H., and Hwang, J.-K. (2006). Ginsenoside 20(S)-protopanax-atriol (PPT) activates peroxisome proliferator-activated receptor y (PPARy) in 3T3-L1 adipocytes. Biol. Pharm. Bull. 29,110-113. 

The farnesoid X receptor is a member of the class of nuclear hormone receptors, which have key roles in development and homeostasis, as well as in many diseases like obesity, diabetes and cancer. The farnesoid X receptor shows structural similarity to the estrogen receptor (ER ), which mediates a broad spectrum of physiological functions such as regulation of reproduction, modulation of bone density, cholesterol transport and breast cancer. The farnesoid X receptor also shows similarity with the peroxisome proliferation-activated receptor y (PPARy), which is involved in fat metabolism, inflammatory and immune responses. The estrogen receptor (ER ), the peroxisome proliferation-activated receptor y (PPARy) and the farnesoid X receptor (FXR) can be clustered in a... 

Research has now established that the peroxisome proliferators act on a receptor, called the peroxisome proliferator-activated receptor (PPAR), discovered in 1990. There are now known to be three receptors PPARa, PPARS, and PPARy. These are parts of the nuclear hormone super family. The PPARs are ligand-dependent transcription factors, which have different functions and tissue locations. 

Lehmann, J. M., Moore, L. B., Smith-Oliver, T. A. et al. (1995). An Antidiabetic Thi-azolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-Activated Receptor y (PPARy). /. Biol. Chem. 270, 12953-12956. 

Rosiglitazone 9, an agonist of peroxisome proliferator activated receptor-y (PPARy), is a recently introduced antihyperglycemic thiazolidinedione effective in the treatment of noninsulin dependant diabetes mellitus (type II diabetes). A seven-step synthesis was developed (Scheme 3), which utilised supported reagents in combination with in-line SPE purifications. The introduction of the pyridine moiety provided a convenient molecular handle by which to purify the molecule throughout the synthesis. Notably, the overall yield (46%) for this synthesis was higher than the yield reported in the initial shorter solution-phase synthesis (31%). ... 

A GRID/CPCA analysis of the three subtypes of Peroxisome Proliferator-Activated Receptors (PPARs) vas reported by Pirard [18] using three PPARa, eight PPARy, and three PPARd X-ray structures of the ligand binding domain (LED). 

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