The effects of insulin on the level and activity of the GLUT4 present in human adipose cells.
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)
Kozka
I J
IJ
School of Biology and Biochemistry, University of Bath, UK.
Clark
A E
AE
Reckless
J P
JP
Cushman
S W
SW
Gould
G W
GW
Holman
G D
GD
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
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