Modulation of PPARγ activity with pharmaceutical agents: Treatment of insulin resistance and atherosclerosis
| Autor: | Sherrie Tafuri, Minghan Wang |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Arteriosclerosis medicine.medical_treatment Population Receptors Cytoplasmic and Nuclear Peroxisome proliferator-activated receptor Estrogen receptor Biology Pharmacology Models Biological Biochemistry Insulin resistance Internal medicine medicine Animals Humans Hypoglycemic Agents education Molecular Biology Foam cell chemistry.chemical_classification education.field_of_study Insulin Cell Biology medicine.disease Thiazoles Endocrinology Diabetes Mellitus Type 2 chemistry Nuclear receptor Adipogenesis Thiazolidinediones Insulin Resistance Transcription Factors |
| Zdroj: | Journal of Cellular Biochemistry. 89:38-47 |
| ISSN: | 1097-4644 0730-2312 |
| Popis: | The anti-diabetic thiazolidinediones (TZDs) are a class of compounds with insulin-sensitizing activity that were originally discovered using in vivo pharmacological screens. In subsequent binding studies, TZDs were demonstrated to enhance insulin action by activating peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ is a member of the ligand-activated nuclear receptor superfamily that promotes adipogenesis and enhances insulin sensitivity by controlling the expression of genes in glucose and lipid metabolism. Given the large size of the ligand binding pocket in PPARγ, novel classes of both full and partial agonists that are structurally distinct from TZDs have been discovered. These compounds have been effective tools in differentiating adipogenic and insulin-sensitizing activities as well as tissue selectivity of PPARγ activation. This information has led to the hypothesis that one ligand can activate or inactivate PPARs depending upon the tissue in which the PPAR resides. Thus particular compounds can be designated selective PPAR modulators or SPPARMs, a concept similar to that observed with the activation of estrogen receptor (ER) by SERMS. Additionally, both preclinical and clinical data suggest that PPARγ activation is useful for the prevention of atherosclerosis. However, the effects of TZDs on plasma lipid profiles do not solely account for their anti-atherogenic effects. Recent studies with macrophage cells and animal models for atherosclerosis indicate that TZDs reduce the size and number of lesions formed in the vessel wall by modulating foam cell formation and inflammatory responses by macrophages. Thus in addition to the treatment of type II diabetes, PPARγ agonists can be potentially employed for the treatment of atherosclerosis in general population. J. Cell. Biochem. 89: 38–47, 2003. © 2003 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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