Insulin peroxisome proliferator-activated

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 . 

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... 

Thiazolidinediones are known to increase insulin sensitivity by stimulating peroxisome proliferator-activated receptor gamma (PPAR-y). Stimulation of PPAR-y results in a number of intracellular and extracellular changes, including an increased number of insulin receptors, increased insulin receptor sensitivity, decreased plasma fatty acid levels, and an increase in a host of intracellular signaling proteins that enhance glucose uptake. 

Peroxisome Proliferator activated receptor (PPAR-GAMMA-2) Insulin Variation of insulin efficacy in the treatment of diabetes (93) Susceptibility to type II diabetes (93)... 

HP-jS-CD were added. All compounds were resolved in 20 min (see Figure 5). The data indicated that the validated method offered equivalent and complementary information, in terms of selectivity, sensitivity, accuracy, linearity, and precision, to that of an established gradient LC method employed for similar purposes. Ragaglitazar is a dual peroxisome proliferator-activated receptor ot and y agonist intended to restore insulin sensitivity and correct diabetic dyslipidemia. A chiral CZE method combining two CDs, sulfobutylether-jS-CD and dimethyl-/i-CD, lent itself to the analysis of ragaglitazar, its distomer (the (+)... 

Thiazolidinediones are the newer agents that favourably influence insulin sensitivity and possibly also pancreatic fS-cell function. The biological response of thiazolidinediones is mediated by binding to the nuclear peroxisome proliferator-activated receptor-y (PPAR)... 

Netoglitazone is an insulin sensitizer currently in Phase II clinical trials. It is able to modulate both PPAR-a and PPAR-y subtypes of peroxisome proliferator-activated receptor (Phase ll). Metaglidasen (MBX-102) is the (—)-enantiomer of the NSAID halofenate. This selective PPAR-y nuclear receptor agonist is being evaluated (Phase II) as an insulin sensitizer. It is structurally different from the currently marketed glitazones (Figure 8.84). ... 

The 3,4-dihydro-22/-l,3-benzoxazin-4-one derivative DRF-2519 587, bearing a 2,4-thiazolidinedione moiety in the side chain attached to the nitrogen atom, proved to be an activator of the a- and y-types of the peroxisome proliferator-activated receptors (PPAR-a and -7), which endowed it with antidiabetic and hypolipidemic potential. Compound 587 demonstrated significant plasma glucose-, insulin-, and lipid-lowering activity in mice and improvement in lipid parameters in fat-fed rats <2006BMC584>. 

Mechanism of Action Potent and highly selective agonist for peroxisome proliferator-activated receptor-gamma (PPAR(gamma)) which decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. 

While the thiazolidindiones enhance insulin-mediated glucose transport via binding to the peroxisome proliferator-activating receptor (PPAR-y), the presence of this receptor in vascular smooth muscle cells, inflammatory cells, and endothelial cells likely facilitates the drug s ability to inhibit vascular smooth muscle cell proliferation, reduce inflammation, improve dyslipidemia, and, by extension, reduce in-stent restenosis. 

Murakami, K., Tobe, K., Ide, T., Mochizuki, T., Ohashi, M., Akanuma, Y., Yazaki, Y., and Kadowaki, T. (1998). A novel insulin sensitizer acts as a coligand for peroxisome proliferator-Activated Receptor-Alpha (PPAR-alpha) and PPAR-Gamma Effect of PPAR-Alpha Activation on Abnormal Lipid Metabolism in Liver of Zucker Fatty Rats. Diabetes AT, 1841-1847. 

Kruszynska, Y. T., Mukheijee, R.,Jow, L., Dana, S., Paterniti,J. R., and 01efsky,J. M. (1998). Skeletal Muscle Peroxisome Proliferator-Activated Receptor-y Expression in Obesity and Non-Insulin-Dependent Diabetes Mellitus. J. Clin. Invest. 101, 543-548. 

Mori, Y., Kim-Motoyama, H., Katakura, T., Yasuda, K., Kadowaki, H., Beamer, B. A., Shuldiner, A. R., Akanuma, Y., Yasaki, Y., and Kadowaki, T. (1998). Effect of the Prol2Ala Variant of the Human Peroxisome Proliferator-Activated Receptor y2 Gene on Adiposity, Fat Distribution, and Insulin Sensitivity in Japanese Men. Biochem. Biophys. Res. Commun. 251, 195-198. 

Hnang B, Wn P, Bowker-Kinley MM, and Harris RA (2002) Regnlation of pyruvate dehydrogenase kinase expression hy peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin. Diabetes 51,276-83. 

Sugden MC, Bulmer K, Augustine D, and Holness MJ (2001a) Selective modification of pyruvate dehydrogenase kinase isoform expression in rat pancreatic islets elicited by starvation and activation of peroxisome proliferator-activated receptor-alpha implications for glucose-stimulated insulin secretion. Diabetes 50, 2729-36. 

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