Renal protective effect of troglitazone in Wistar fatty rats

Although it is known that renal injury develops in obesity and diabetes mellitus, there have been no investigations examining the impact of insulin resistance per se on the development of renal injury. The present study was undertaken to examine whether insulin resistance and obesity influence urinary protein excretion (UPE) in female heminephrectomized Wistar fatty rats (WFRs). After 24 weeks of heminephrectomy in WFRs, the body weight ([BW], 465+/-18 g; n = 6), blood pressure (155+/-5 mm Hg), serum insulin to glucose ratio (1.31+/-0.39 microU/mg), and daily UPE (24+/-7 mg/d) were greater versus Wistar lean rats ([WLRs] 258+/-8 g, 134+/-1 mm Hg, 0.19+/-0.06 microU/mg, and 5+/-1 mg/d, respectively; n = 6), whereas blood glucose levels did not increase significantly. In WFRs, long-term (ie, 24 weeks) treatment with troglitazone, an insulin-sensitizing agent, improved the serum insulin to glucose ratio (0.17+/-0.09 microU/mg), reduced blood pressure (to 140+/-4 mm Hg), and decreased UPE (to 7+/-1 mg/d), although it had no effect on BW. Of note, with troglitazone treatment, the reduction in proteinuria preceded the correction of hypertension (ie, at week 12). In conclusion, our study suggests that insulin resistance per se causes proteinuria that does not appear to depend on blood pressure. Furthermore, long-term therapy with troglitazone may be a useful tool for the treatment of renal injury in the insulin-resistant condition.