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[The chemical structure and pharmacological properties of a novel isoxazolidinedione insulin sensitizer, JTT-501].

JTT-501 is an isoxazolidine-3,5-dione derivative. This drug activates both PPAR gamma and PPAR alpha, and shows not only a hypoglycemic effect but also a stronger triglyceride-lowering effect than the thiazolidine-2,4-diones. JTT-501 improved both the impaired insulin-stimulated autophosphorylation levels of Zucker fatty rats and impaired insulin-induced GLUT4 translocation to the plasma membrane as well as insulin-induced glucose uptake in high fat diet rats, indicating that JTT-501 enhances insulin signaling and reduces insulin resistance. Furthermore, JTT-501 prevented several diabetic complications, such as cataract, nephropathy, and neuropathy in Zucker diabetic fatty rats. As a non-thiazolidinedione insulin sensitizer, JTT-501 has been the first to start clinical trials and is currently undergoing evaluation in clinical studies for diabetic patients.