Shinkai H
Central Pharmaceutical Research Institute, Japan Tobacco Inc.
Nihon Rinsho. 2001 Nov;59(11):2207-10.
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.
JTT - 501是一种异恶唑烷 - 3,5 - 二酮衍生物。这种药物可同时激活过氧化物酶体增殖物激活受体γ（PPARγ）和过氧化物酶体增殖物激活受体α（PPARα），不仅具有降血糖作用，而且与噻唑烷 - 2,4 - 二酮类药物相比，还具有更强的降低甘油三酯的作用。JTT - 501改善了Zucker肥胖大鼠胰岛素刺激的自磷酸化水平受损以及高脂肪饮食大鼠中胰岛素诱导的葡萄糖转运蛋白4（GLUT4）转位至质膜受损的情况，以及胰岛素诱导的葡萄糖摄取，这表明JTT - 501增强了胰岛素信号传导并降低了胰岛素抵抗。此外，JTT - 501预防了Zucker糖尿病肥胖大鼠的几种糖尿病并发症，如白内障、肾病和神经病变。作为一种非噻唑烷二酮类胰岛素增敏剂，JTT - 501是首个开始临床试验的药物，目前正在针对糖尿病患者进行临床研究评估。
