Disease relevance of Darglitazone

• Similar effects on adipose tissue, hemodilution, and edema (peripheral and pulmonary) were observed clinically with darglitazone and/or several other structurally similar/dissimilar PPAR-gamma agonists [1].

High impact information on Darglitazone

• Detailed studies were conducted with darglitazone, which under basal conditions increased Ra (+114%), Rox (+51%), and Rfs in adipose tissues [2].
• After 24 h of exposing HIB-1B brown adipocytes to 30 micromol/l darglitazone or 20 micromol/l troglitazone, beta3-AR mRNA levels were reduced by 75% [3].
• The darglitazone ID50 was approximately 10 nmol/l, similar to the Kd of TZDs binding to peroxisome proliferator-activated receptor-gamma (PPAR-gamma) [3].
• Darglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma ligand, neutralized the NEFA-mediated induction of the decorin gene [4].
• Metabolic effects of darglitazone, an insulin sensitizer, in NIDDM subjects [5].

Biological context of Darglitazone

• CONCLUSION AND CLINICAL RELEVANCE: The response of obese cats to darglitazone was similar to the response to thiazolidinediones in obese humans and rodents Darglitazone was effective in improving insulin sensitivity and glucose and lipid metabolism in obese cats [6].

Anatomical context of Darglitazone

• Therefore we tested the effect of fatty acids and how fatty acids and the thiazolidinedione darglitazone interact in their effect on CD36 expression in human monocytes and macrophages [7].

Associations of Darglitazone with other chemical compounds

• In all cells TZDs (darglitazone, troglitazone) were more active than the predominantly PPAR alpha ligands WY-14,613 and clofibrate, or the non-selective ligand linoleic acid [8].
• In the presence of 5% human serum, darglitazone increased the accumulation of triglycerides, but did not affect cholesterol ester levels [7].
• RESULTS: Darglitazone-treated cats had significantly lower cholesterol, triglyceride, and leptin concentrations, compared with placebo-treated obese cats [6].

Gene context of Darglitazone

• Furthermore, the PPARgamma agonists 9-hydroxy-(S)-10,12-octadecadienoic acid (9-HODE) and darglitazone also decreased VEGFR-1 mRNA expression [9].
• RESULTS: Darglitazone increased CD36 mRNA and protein expression in human macrophage cells [7].
• Within 4 h of exposing these cells to 30 microM darglitazone, there was an increase in UCP2 mRNA which reached a plateau of 5-10 times the basal in about 8 h [8].
• Treatment of mature adipocytes with t10,c12 CLA alone or in combination with Darglitazone down-regulates the mRNA expression of PPARgamma as well as its target genes, fatty acid binding protein (aP2) and liver X receptor alpha (LXRalpha) [10].
• A TZD, darglitazone (darg), can rapidly induce differentiation of HIB-1B cells, as judged by the expression of the adipocyte lipid binding protein (aP2), lipoprotein lipase (LPL), uncoupling protein (UCP) and beta3-adrenergic receptors [11].

References