[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.
Shinkai
H
H
Central Pharmaceutical Research Institute, Japan Tobacco Inc.
D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000517:prevention & control; D003929:Diabetic Neuropathies / Q000517:prevention & control; D051275:Glucose Transporter Type 4; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000819:agonists
D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D007555:Isoxazoles; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C495692:SLC2A4 protein, human; C495694:Slc2a4 protein, rat; D014157:Transcription Factors; C112329:JTT 501