The role of peroxisome proliferator-activated receptor gamma in diabetes and obesity.

被引：63
作者：
Celi F.S. [1 ]
Shuldiner A.R. [1 ]
机构：
[1] University of Maryland School of Medicine, Division of Endocrinology, Diabetes and Nutrition, Room, 660 West Redwood Street, Baltimore, 21201, MD
来源：
Current Diabetes Reports | 2002年 / 2卷 / 2期
关键词：
Troglitazone; Retinoic Acid Receptor; Thyroid Hormone Receptor; Increase Insulin Sensitivity; Adipose Tissue Mass;
D O I：
10.1007/s11892-002-0078-2
中图分类号：
学科分类号：
摘要：
Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor, which upon activation with various natural and synthetic ligands, stimulates the transcription of genes responsible for growth and differentiation of adipocytes. Furthermore, PPAR gamma is the receptor for the insulin-sensitizing thiazolidinediones, which are commonly used for the treatment of type 2 diabetes. Rare inactivating mutations of the gene encoding PPAR gamma are associated with insulin resistance type 2 diabetes, and hypertension, whereas a rare gain of function mutation causes extreme obesity. A common polymorphism (Pro12Ala) of the adipose tissue-specific gamma 2 isoform is associated with increased insulin sensitivity and decreased risk of developing type 2 diabetes. These findings indicate a central role of PPAR gamma in fat cell biology and in the pathophysiology of obesity, diabetes, and insulin resistance.
引用
收藏
页码：179 / 185
页数：6
相关论文
共 174 条
[21]  
Fajas L(2001)A role for C/EBPbeta in regulating peroxisome proliferator-activated receptor gamma activity during adipogenesis in 3T3-L1 preadipocytes J Biol Chem 276 18464-18471
[22]  
Auwerx J(1999)Insulin acutely regulates the expression of the peroxisome proliferatoractivated receptor-gamma in human adipocytes Diabetes 48 699-705
[23]  
Fajas L(1997)Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma Proc Natl Acad Sci U S A 94 4318-4323
[24]  
Debril MB(1997)Ligand-independent activation domain in the N terminus of peroxisome proliferator-activated receptor gamma (PPARgamma). Differential activity of PPARgamma1 and -2 isoforms and influence of insulin J Biol Chem 272 20230-20235
[25]  
Auwerx J(2001)Thiazolidinediones and liver toxicity Diabetes Metab 27 305-313
[26]  
Ricote M(1998)Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats J Clin Invest 101 1354-1361
[27]  
Huang JT(1997)Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation J Clin Invest 100 3149-3153
[28]  
Welch JS(1995)Repeat treatment of obese mice with BRL 49653, a new potent insulin sensitizer, enhances insulin action in white adipocytes. Association with increased insulin binding and cell-surface GLUT4 as measured by photoaffinity labeling Diabetes 44 1087-1092
[29]  
Glass CK(2001)Thiazolidinediones (PPARgamma agonists) but not PPARalpha agonists increase IRS-2 gene expression in 3T3-L1 and human adipocytes FASEB J 15 215-220
[30]  
Kersten S(2001)Plasma fatty acids, adiposity, and variance of skeletal muscle insulin resistance in type 2 diabetes mellitus J Clin Endocrinol Metab 86 5412-5419
12345678910