The effects of wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, on insulin-stimulated glucose transport, GLUT4 translocation, antilipolysis, and DNA synthesis
| Autor: | Barbara E. Womelsdorf, Christian M. Honer, Emma L. Kaplan, Philip A. Bell, Joseph L. Evans |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
DNA Replication
medicine.medical_specialty Antifungal Agents Monosaccharide Transport Proteins Lipolysis medicine.medical_treatment Muscle Proteins Biology Rats Sprague-Dawley Wortmannin Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound Liver Neoplasms Experimental Internal medicine Adipocytes Tumor Cells Cultured medicine Animals Insulin Inositol Phosphatidylinositol Enzyme Inhibitors Muscle Skeletal Cells Cultured Glucose Transporter Type 4 Dose-Response Relationship Drug DNA synthesis Glucose transporter Biological Transport 3T3 Cells DNA Cell Biology Mycotoxins Rats Androstadienes Phosphotransferases (Alcohol Group Acceptor) Glucose Endocrinology chemistry biology.protein GLUT1 GLUT4 |
| Zdroj: | Cellular Signalling. 7:365-376 |
| ISSN: | 0898-6568 |
| DOI: | 10.1016/0898-6568(95)00007-c |
| Popis: | PI 3-kinase, an enzyme that selectively phosphorylates the 3-position of the inositol ring, is acutely activated by insulin and other growth factors. The physiological significance of PI 3-kinase activation and, more specifically, its role in insulin action is an area under intense investigation. In this study, we have examined the role of PI 3-kinase activation in mediating selected metabolic and mitogenic effects of insulin employing the fungal metabolite wortmannin, a potent inhibitor of PI 3-kinase activity. In isolated rat and cultured 3T3-L1 adipocytes, wortmannin inhibited insulin-stimulated glucose transport ( ic 50 = 9 nM) without a significant effect on basal transport. Insulin-stimulated translocation of GLUT4 in isolated rat adipocytes was markedly inhibited by wortmannin. Wortmannin had no effect on either basal or insulin-stimulated glucose utilization in L6 myocytes, a skeletal muscle cell line in which GLUT1 is the predominant transporter isoform. Wortmannin also partially antagonized the antilipolytic effect of insulin on adenosine deaminase-stimulated lipolysis in isolated rat adipocytes. Furthermore, wortmannin caused a significant reduction in insulin-stimulated DNA synthesis in Fao rat hepatoma cells. We conclude that PI 3-kinase activation is necessary for maximum insulin-stimulated glucose transport, translocation of GLUT4, antilipolysis and DNA synthesis. |
| Databáze: | OpenAIRE |
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