Effects of peroxisome proliferator-activated receptor-α and -γ agonist, JTT-501, on diabetic complications in Zucker diabetic fatty rats

1 This study has investigated the effects of JTT-501, a peroxisome proliferator-activated receptor (PPBR)-alpha and PPAR-gamma; agonist, on the pathogenesis of diabetic complications in the Zucker diabetic fatty (ZDF) rats, a model of type 2 diabetes. Comparison is made with troglitazone, a PPAR-gamma agonist. 2 The ZDF rats exhibited hyperglycaemia and hyperlipidaemia, and developed diabetic complications such as cataract, nephropathy, and neuropathy. Treatment with JTT-501 from the prediabetic stage controlled glycaemia and lipidaemia, and prevented the development of diabetic complications. Troglitazone was less effective in controlling serum cholesterol and neuropathy. 3 ZDF rats developed diabetic osteopenia with reduced bone turnover. and this was prevented by JTT-501 and troglitazone, possibly mediated by increased bone turnover and bone formation. 4 Since JTT-501 controlled glycaemia and lipidaemia in ZDF rats and prevented several diabetic complications. it is suggested that treatment with JTT-501, which activates both PPAR-alpha and PPAR-gamma, could provide a valuable therapeutic approach against diabetic complications in type 2 diabetes.