31 Heart, E. Sung, C. K. 2003 J Cell Biochem 88 4 719-31 Mar 1 0730-2312 (Print) 12577306 Insulin Antagonists/pharmacology Insulin/pharmacology/physiology Glucose Transporter Type 1 Glucose/metabolism/pharmacology Enzyme Inhibitors/pharmacology Enzyme Activation/drug effects Dose-Response Relationship, Drug Deoxyglucose/metabolism Cell Membrane/metabolism Animals Androstadienes/pharmacology Adipocytes 3T3 Cells 1-Phosphatidylinositol 3-Kinase/antagonists & inhibitors/metabolism Time Factors Signal Transduction/drug effects Selenium/pharmacology/*physiology Phosphorylation/drug effects Monosaccharide Transport Proteins/antagonists & inhibitors/metabolism Mice Lipolysis/drug effects/physiology Dose-Response Relationship Drug In insulin-sensitive 3T3-L1 adipocytes, selenium stimulates glucose transport and antilipolysis and these actions of selenium, like insulin actions, are sensitive to wortmanin, an inhibitor of phosphatidylinositol-3-kinase (PI3K). Selenium stimulates PI3K activity that is sustained up to 24 h. Selenium after 5-10 min increases tyrosine phosphorylation of selective cellular proteins, but after 24 h overall tyrosine phosphorylation is increased. Tyrosine phosphorylation of insulin receptor substrate 1 is detected when enriched by immunoprecipitation with anti-PI3K antibody. Selenium, however, does not stimulate insulin receptor tyrosine kinase activity. Selenium also increases phosphorylation of other insulin signaling proteins, including Akt and extracellular signal regulated kinases. Selenium-stimulated glucose transport is accompanied by increases in glucose transporter-1 content in the plasma membrane. These data are consistent with similar selenium action in glucose transport in 3T3-L1 fibroblasts expressing mainly GLUT1. In chronic insulin-induced insulin resistant cells, selenium unlike insulin fully stimulates glucose transport. In summary, selenium stimulates glucose transport and antilipolysis in a PI3K-dependent manner, but independent of insulin receptor activation. Selenium exerts both insulin-like and non-insulin-like actions in cells. DK51015/DK/NIDDK NIH HHS/United StatesComparative StudyJournal ArticleResearch Support, U.S. Gov't, P.H.S.United States http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12577306