title: The effects of insulin on the level and activity of the GLUT4 present in human adipose cells.
abstract: Human adipose cells are much less responsive to insulin stimulation of glucose transport activity than are rat adipocytes. To assess and characterize this difference, we have determined the rates of 3-O-methyl-D-glucose transport in human adipose cells and have compared these with the levels of glucose transporter 4 (GLUT4) assessed by using the bis-mannose photolabel, 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(D-mannos- 4-yloxy)-2-propyl-amine, ATB-BMPA. The rates of 3-O-methyl-D-glucose transport and the cell-surface level of GLUT4 are very similar in the human and rat adipocyte in the basal state. The Vmax for 3-O-methyl-D-glucose transport in fully insulin-stimulated human adipose cells is 15-fold lower than in rat adipose cells. Photolabelling of GLUT4 suggests that this low transport activity is associated with a low GLUT4 abundance (39 x 10(4) sites/cell; 19.9 x 10(4) sites at the cell surface). The turnover number for human adipose cell GLUT4 (5.8 x 10(4) min-1) is similar to that observed for GLUT4 in rat adipose cells and the mouse cell line, 3T3L1. Since 50% of the GLUT4 is at the cell surface of both human and rat adipose cells in the fully insulin-stimulated state, an inefficient GLUT4 exocytosis process cannot account for the low transport activity. The intracellular retention process appears to have adapted to release, in the basal state, a greater proportion of the total-cellular pool of GLUT4 to the cell surface of the larger human adipocytes. These cell-surface transporters are presumably necessary to provide the basal metabolic needs of the adipocyte.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: School of Biology and Biochemistry, University of Bath, UK.
authors.forename: I J
authors.initials: IJ
authors.lastname: Kozka
authors.forename: A E
authors.initials: AE
authors.lastname: Clark
authors.forename: J P
authors.initials: JP
authors.lastname: Reckless
authors.forename: S W
authors.initials: SW
authors.lastname: Cushman
authors.forename: G W
authors.initials: GW
authors.lastname: Gould
authors.forename: G D
authors.initials: GD
authors.lastname: Holman
mesh_terms: D019325:3-O-Methylglucose; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D000345:Affinity Labels; D000818:Animals; D001386:Azides / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D002478:Cells, Cultured; D004187:Disaccharides / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D006027:Glycosides; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008757:Methylglucosides / Q000378:metabolism / Q000494:pharmacology; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000302:isolation & purification / Q000378:metabolism*; D009124:Muscle Proteins; D011437:Propylamines; D051381:Rats
chemical_list: D000345:Affinity Labels; D001386:Azides; D004187:Disaccharides; D051275:Glucose Transporter Type 4; D006027:Glycosides; D007328:Insulin; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011437:Propylamines; C495692:SLC2A4 protein, human; C495694:Slc2a4 protein, rat; C065412:2-N-(4-(1-azitrifluoroethyl)benzoyl)-1,3-bis-(mannos-4-yloxy)-2-propylamine; D019325:3-O-Methylglucose; D005947:Glucose