Linked Life Data

16682454

Source:http://linkedlifedata.com/resource/pubmed/id/16682454

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pubmed-article:16682454pubmed:abstractTextAdipogenesis is an important process for the improvement of insulin resistance by peroxisome proliferator-activated receptor (PPAR) gamma agonists, such as rosiglitazone and pioglitazone. FK614 [3-(2,4-dichlorobenzyl)-2-methyl-N-(pentylsulfonyl)-3-Hbenzimidazole-5-carboxamide] is a structurally novel class of PPARgamma agonist that improves insulin sensitivity in animal models of type 2 diabetes. Herein, we characterize FK614, a selective PPARgamma modulator (SPPARM) with differential properties affecting the regulation of fat cell function. FK614 behaves as a partial agonist in inducing the interaction of PPARgamma with both transcriptional coactivators, cAMP response element-binding protein-binding protein and steroid receptor coactivator-1, but as a full agonist with both PPAR-binding protein and PPAR-interacting protein, which are required for PPARgamma-mediated adipogenesis. In the differentiating 3T3-L1 adipocytes, the levels of adipose fatty acid-binding protein (aP2) mRNA expression and triglyceride accumulation induced by FK614 were as efficacious as those of rosiglitazone and pioglitazone. In contrast, the effect of FK614 on aP2 gene expression in mature adipocytes was less than that of the other PPARgamma agonists. Furthermore, the long-term treatment of mature adipocytes with rosiglitazone and pioglitazone reduced the expression of phosphodiesterase 3B, the down-regulation of which has an important role in the development of insulin resistance; however, FK614 had no such effect in mature adipocytes. Thus, FK614 behaves as an SPPARM with differential effects on the activation of PPARgamma at each stage of adipocyte differentiation. The stage-dependent selectivity of FK614 may contribute to its enhanced insulin sensitization in differentiating adipocytes and to reduced insulin resistance at the stage of adipocyte hypertrophy.lld:pubmed
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pubmed-article:16682454pubmed:authorpubmed-author:FujimuraTakao...lld:pubmed
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pubmed-article:16682454pubmed:authorpubmed-author:KimuraChiakiClld:pubmed
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pubmed-article:16682454pubmed:dateRevised2007-11-15lld:pubmed
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pubmed-article:16682454pubmed:year2006lld:pubmed
pubmed-article:16682454pubmed:articleTitleA selective peroxisome proliferator-activated receptor gamma modulator with distinct fat cell regulation properties.lld:pubmed
pubmed-article:16682454pubmed:affiliationMolecular Medicine Research Laboratories, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan. takao.fujimura@jp.astellas.comlld:pubmed
pubmed-article:16682454pubmed:publicationTypeJournal Articlelld:pubmed
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