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

Abstract

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.

• Authors: H Shinkai
• Journal: Nihon rinsho. Japanese journal of clinical medicine (Nihon Rinsho) Vol. 59 Issue 11 Pg. 2207-10 (Nov 2001) ISSN: 0047-1852 [Print] Japan
• PMID: 11712409 (Publication Type: Journal Article, Review)

Chemical References

• Glucose Transporter Type 4
• Hypoglycemic Agents
• Insulin
• Isoxazoles
• Monosaccharide Transport Proteins
• Muscle Proteins
• Receptors, Cytoplasmic and Nuclear
• SLC2A4 protein, human
• Slc2a4 protein, rat
• Transcription Factors
• JTT 501

Topics

• Animals
• Diabetes Mellitus (drug therapy, physiopathology)
• Diabetic Angiopathies (prevention & control)
• Diabetic Neuropathies (prevention & control)
• Glucose Transporter Type 4
• Humans
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Insulin (physiology)
• Insulin Resistance
• Isoxazoles (pharmacology, therapeutic use)
• Monosaccharide Transport Proteins (metabolism)
• Muscle Proteins
• Rats
• Receptors, Cytoplasmic and Nuclear (agonists)
• Signal Transduction (drug effects)
• Transcription Factors (agonists)