31 Heart, E. Choi, W. S. Sung, C. K. 2000 Am J Physiol Endocrinol Metab 278 1 E103-12 Jan 0193-1849 (Print) 10644543 Receptor, Insulin/metabolism Proto-Oncogene Proteins c-akt Proto-Oncogene Proteins/metabolism *Protein-Serine-Threonine Kinases Phosphorylation/drug effects Phosphoproteins/metabolism *Muscle Proteins Monosaccharide Transport Proteins/metabolism Mice Intracellular Signaling Peptides and Proteins *Insulin Resistance Insulin Receptor Substrate Proteins Insulin/pharmacology Glucose Transporter Type 4 Glucosamine/*pharmacology Dose-Response Relationship, Drug Deoxyglucose/pharmacokinetics Cell Membrane/metabolism Animals Adipocytes/*drug effects/*physiology 3T3 Cells 1-Phosphatidylinositol 3-Kinase/metabolism Tyrosine/metabolism Ribosomal Protein S6 Kinases/metabolism Receptor Insulin/metabolism Dose-Response Relationship Drug To study molecular mechanisms for glucosamine-induced insulin resistance, we induced complete and reversible insulin resistance in 3T3-L1 adipocytes with glucosamine in a dose- and time-dependent manner (maximal effects at 50 mM glucosamine after 6 h). In these cells, glucosamine impaired insulin-stimulated GLUT-4 translocation. Glucosamine (6 h) did not affect insulin-stimulated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 and -2 and weakly, if at all, impaired insulin stimulation of phosphatidylinositol 3-kinase. Glucosamine, however, severely impaired insulin stimulation of Akt. Inhibition of insulin-stimulated glucose transport was correlated with that of Akt activity. In these cells, glucosamine also inhibited insulin stimulation of p70 S6 kinase. Glucosamine did not alter basal glucose transport and insulin stimulation of GLUT-1 translocation and mitogen-activated protein kinase. In summary, glucosamine induced complete and reversible insulin resistance in 3T3-L1 adipocytes. This insulin resistance was accompanied by impaired insulin stimulation of GLUT-4 translocation and Akt activity, without significant impairment of upstream molecules in insulin-signaling pathway. R29-DK-51015/DK/NIDDK NIH HHS/United StatesJournal ArticleResearch Support, Non-U.S. Gov'tResearch 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=10644543