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Differential effects of rexinoids and thiazolidinediones on metabolic gene expression in diabetic rodents.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Ahuja, H. Singh Liu, Shengxi Crombie, Diane L. Böhm, Michael Leibowitz, Mark D. Heyman, Richard A. Depré, Christophe Nagy, László Tontonoz, Peter Davies, Peter |
| Copyright Year | 2001 |
| Abstract | Both retinoid X receptor (RXR)-selective agonists (rexinoids) and thiazolidinediones (TZDs), PPAR (peroxisome proliferator-activated receptor)-gamma-specific ligands, produce insulin sensitization in diabetic rodents. In vitro studies have demonstrated that TZDs mediate their effects via the RXR/PPAR-gamma complex. To determine whether rexinoids lower hyperglycemia by activating the RXR/PPAR-gamma heterodimer in vivo, we compared the effects of a rexinoid (LG100268) and a TZD (rosiglitazone) on gene expression in white adipose tissue, skeletal muscle, and liver of Zucker diabetic fatty rats (ZDFs). In adipose tissue, rosiglitazone decreased tumor necrosis factor-alpha (TNF-alpha) mRNA and induced glucose transporter 4 (GLUT4), muscle carnitine palmitoyl-transferase (MCPT), stearoyl CoA desaturase (SCD1), and fatty acid translocase (CD36). In contrast, LG100268 increased TNF-alpha and had no effect or suppressed the expression of GLUT4, MCPT, SCD1, and CD36. In liver, the rexinoid increased MCPT, SCD1, and CD36 mRNAs, whereas rosiglitazone induced only a small increase in CD36. In skeletal muscle, rosiglitazone and LG100268 have similar effects; both increased SCD1 and CD36 mRNAs. The differences in the pattern of genes induced by the rexinoids and the TZDs in diabetic animals found in these studies suggests that these compounds may have independent and tissue-specific effects on metabolic control in vivo. |
| Starting Page | 199 |
| Ending Page | 218 |
| Page Count | 20 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://molpharm.aspetjournals.org/content/molpharm/59/4/765.full.pdf |
| PubMed reference number | 11259621v1 |
| Volume Number | 59 |
| Issue Number | 4 |
| Journal | Molecular pharmacology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Carnitine O-Palmitoyltransferase Diabetes Mellitus Fatty Acids Fatty Liver Gene Expression Glucose Metabolism Disorders Glucose Transporter Hyperglycemia Interferon Type II Interleukin Receptor Common gamma Subunit LG 100268 Ligands Metabolic Process, Cellular Palmitoyl-CoA Hydrolase Peroxisome Proliferators Platelet Glycoprotein 4, human Renal carnitine transport defect Retinoid X Receptors Retinoids Rodent SCD gene SCD wt Allele SLC2A4 gene Sensitization (observable entity) Skeletal muscle structure Thiazolidinediones Transferase Tumor Necrosis Factors White Adipose Tissue Z, Rat Strain alpha-Mannosidosis rosiglitazone |
| Content Type | Text |
| Resource Type | Article |
