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

1 This study has investigated the effects of JTT-501, a peroxisome prolifer ator-activated receptor (PPBR)-alpha and PPAR-gamma; agonist, on the pathog enesis 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 T he ZDF rats exhibited hyperglycaemia and hyperlipidaemia, and developed dia betic complications such as cataract, nephropathy, and neuropathy. Treatmen t with JTT-501 from the prediabetic stage controlled glycaemia and lipidaem ia, and prevented the development of diabetic complications. Troglitazone w as less effective in controlling serum cholesterol and neuropathy. 3 ZDF rats developed diabetic osteopenia with reduced bone turnover. and th is was prevented by JTT-501 and troglitazone, possibly mediated by increase d bone turnover and bone formation. 4 Since JTT-501 controlled glycaemia and lipidaemia in ZDF rats and prevent ed several diabetic complications. it is suggested that treatment with JTT- 501, which activates both PPAR-alpha and PPAR-gamma, could provide a valuab le therapeutic approach against diabetic complications in type 2 diabetes.