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

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.

Renoprotective Effect of Pioglitazone by the Prevention of Glomerular Hyperfiltration through the Possible Restoration of Altered Macula Densa Signaling in Rats with Type 2 Diabetic Nephropathy

“…Consequently, whether or not systemic blood pressure is correlated with the renoprotective effect of PGZ is a significant issue. The effect of TZD on blood pressure is still controversial, dependent on individual reports [29]. In the present study, it was clearly shown that systemic blood pressure was not affected by the administration of PGZ for 2 weeks.…”

Effects of PPAR.GAMMA. on hypertension, atherosclerosis, and chronic kidney disease

“…These findings are potentially interesting in terms of pathophysiology, since TZDs have been reported to expand body fluid volume through PPARγ stimulation of the epithelial Na + channel-mediated renal salt absorption [32]. Reno-protective effects of PPARγ ligands on type 2 diabetic patients with nephropathy, especially their effects on reducing urinary albumin, have recently been reported [33]. Additionally, similar effects have been observed in animal experiments using various rodent models of type 2 diabetes [33].…”

“…Reno-protective effects of PPARγ ligands on type 2 diabetic patients with nephropathy, especially their effects on reducing urinary albumin, have recently been reported [33]. Additionally, similar effects have been observed in animal experiments using various rodent models of type 2 diabetes [33]. The mechanisms by which PPARγ ligands reduce urinary albumin remain unclear.…”

Change in Albuminuria and eGFR Following Insulin Sensitization Therapy Versus Insulin Provision Therapy in the BARI 2D Study

“…Sobel et al (15) reported that, in BARI 2D subjects, IS as opposed to IP treatment led to changes in biomarker profiles that were indicative of a profibrinolytic, antithrombotic, and antiinflammatory state. Peroxisome proliferator-activated receptors are widely expressed in the kidney, and peroxisome proliferator-activated receptor gamma agonists have renoprotective effects in experimental models of diabetic kidney disease (16,17). Administration of TZDs to insulin-deficient and -resistant diabetic rats ameliorated albuminuria and histologic hallmarks of diabetic nephropathy (18,19).…”