Differential control of the functional cell surface expression and content of hexose transporter GLUT-1 by glucose and glucose metabolism in murine fibroblasts.
The present paper evaluates the contributions of glucose and its metabolites to the post-translational regulation of hexose transport and GLUT-1 content in murine fibroblasts. The effects of 3-O-methylglucose, a nearly non-metabolizable glucose analogue, on 2-deoxyglucose-uptake, cell-surface expression and content of GLUT-1, glucose 6-phosphate levels, and phosphoglucose isomerase (PGI) and hexokinase activities of murine fibroblasts were compared with those of glucose and fructose. Glucose (EC50 approximately 6 mM) or 3-O-methylglucose (EC50 approximately 12 mM), which are substrates of GLUT-1, but not fructose, which is not transported by GLUT-1, are able to prevent the glucose-deprivation-induced increases in both hexose transport and cell-surface expression of GLUT-1. In contrast, glucose (EC50 approximately 6 mM), but not 3-O-methylglucose or fructose, prevents the glucose-deprivation-induced accumulation of total GLUT-1 polypeptides. Glucose (> or = 5 mM), but not fructose or 3-O-methylglucose, leads to significant glucose 6-phosphate accumulation. Although 3-O-methylglucose is weakly phosphorylated by fibroblasts, accumulation of phosphorylated product does not correlate with hexose-transport regulation. The activities of hexokinase and PGI are not altered by glucose, fructose or 3-O-methylglucose. We suggest that, in murine fibroblasts: (i) hexose transport and GLUT-1 content are differentially regulated; (ii) substrates of GLUT-1 and/or their immediate metabolites regulate the cell-surface expression of functional GLUT-1; and (iii) glucose metabolism is required for the regulation of GLUT-1 content.
Ortiz
P A
PA
Department of Physiology and Biophysics, State University of New York, Stony Brook 11794-8661.
Haspel
H C
HC
D019325:3-O-Methylglucose; D016475:3T3 Cells; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005632:Fructose / Q000378:metabolism / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D051272:Glucose Transporter Type 1; D019298:Glucose-6-Phosphate; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism; D005958:Glucosephosphates / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D006601:Hexoses / Q000378:metabolism* / Q000494:pharmacology*; D008757:Methylglucosides / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects
D051272:Glucose Transporter Type 1; D005958:Glucosephosphates; D006601:Hexoses; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; C495678:Slc2a1 protein, mouse; D019325:3-O-Methylglucose; D005632:Fructose; D019298:Glucose-6-Phosphate; D006593:Hexokinase; D005956:Glucose-6-Phosphate Isomerase; D005947:Glucose