Role of PPARgamma in renoprotection in Type 2 diabetes: molecular mechanisms and therapeutic potential

Clin Sci (Lond). 2009 Jan;116(1):17-26. doi: 10.1042/CS20070462.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adiponectin / metabolism
  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / prevention & control*
  • Disease Models, Animal
  • Humans
  • Insulin Resistance
  • Kidney / metabolism
  • Lipid Metabolism / drug effects
  • Mice
  • PPAR gamma / metabolism
  • PPAR gamma / physiology*
  • Rats
  • Thiazolidinediones / therapeutic use

Substances

  • Adiponectin
  • Anti-Inflammatory Agents
  • PPAR gamma
  • Thiazolidinediones