Role of PPARgamma in renoprotection in Type 2 diabetes: molecular mechanisms and therapeutic potential.
DN (diabetic nephropathy) is a chronic disease characterized by proteinuria, glomerular hypertrophy, decreased glomerular filtration and renal fibrosis with loss of renal function. DN is the leading cause of ESRD (end-stage renal disease), accounting for millions of deaths worldwide. TZDs (thiazolidinediones) are synthetic ligands of PPARgamma (peroxisome-proliferator-activated receptor gamma), which is involved in many important physiological processes, including adipose differentiation, lipid and glucose metabolism, energy homoeostasis, cell proliferation, inflammation, reproduction and renoprotection. A large body of research over the past decade has revealed that, in addition to their insulin-sensitizing effects, TZDs play an important role in delaying and preventing the progression of chronic kidney disease in Type 2 diabetes. Although PPARgamma activation by TZDs is in general considered beneficial for the amelioration of diabetic renal complications in Type 2 diabetes, the underlying mechanism(s) remains only partially characterized. In this review, we summarize and discuss recent findings regarding the renoprotective effects of PPARgamma in Type 2 diabetes and the potential underlying mechanisms.
Yang
Jichun
J
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100083, China.
Zhang
Dongjuan
D
Li
Jing
J
Zhang
Xiaoyan
X
Fan
Fenling
F
Guan
Youfei
Y
D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006801:Humans; D007333:Insulin Resistance; D007668:Kidney / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D045162:Thiazolidinediones / Q000627:therapeutic use
D052242:Adiponectin; D000893:Anti-Inflammatory Agents; D047495:PPAR gamma; D045162:Thiazolidinediones