title: The hemopoietic growth factor, interleukin-3, promotes glucose transport by increasing the specific activity and maintaining the affinity for glucose of plasma membrane glucose transporters.
abstract: Most mammalian cells rely on an external supply of glucose for survival, proliferation, and function. Glucose enters cells through specific transporter molecules at the plasma membrane by a facilitative process that does not expend energy. Regulation of glucose transport into cells is thought to occur largely through transporter expression at the cell surface, but the extent to which the intrinsic properties of glucose transporters are regulated is at present controversial. Using a bone marrow-derived cell line that responds to the hemopoietic growth factor, interleukin-3 (IL-3), we investigated IL-3 regulation of glucose transport. IL-3 significantly increased 2-deoxyglucose (2-DOG) uptake within 1 h (26 +/- 8.0%, n = 11) with a maximum 73% increase after 6 h. Withdrawal of IL-3 resulted in decreased uptake within 1 h and this continued to decline to 43% of initial uptake by 16 h. To determine whether these changes in 2-DOG uptake were associated with corresponding changes in glucose transporter expression, subtype-specific antisera against Glut-1 and Glut-3 were used. Little change in membrane expression of these transporters was observed prior to 16 h. Fractionation of cell membranes on Nycodenz gradients showed that the majority of each transporter subtype was associated with the plasma membrane (63-93%) and that transporter distribution did not change markedly in response to addition or withdrawal of IL-3. These results demonstrate that IL-3 regulates glucose uptake by modulating the intrinsic transporting ability of glucose transporters. Decreased transporter affinity for 2-DOG and 3-O-methylglucose was observed following IL-3 withdrawal. Similar affinity changes were observed with 2-DOG following exposure of IL-3-stimulated cells to the protein kinase inhibitors, genistein and staurosporine. In contrast, the tyrosine phosphatase inhibitor, vanadate, acted like IL-3 to increase transporter affinity for glucose. Together these results demonstrate that IL-3 acts to maintain the intrinsic transport properties of glucose transporters without markedly affecting their expression or translocation.
authors.affiliation: Malaghan Institute of Medical Research, Wellington School of Medicine, P. O. Box 7060, Wellington South 6002, New Zealand.
authors.forename: K D
authors.initials: KD
authors.lastname: McCoy
authors.forename: N
authors.initials: N
authors.lastname: Ahmed
authors.forename: A S
authors.initials: AS
authors.lastname: Tan
authors.forename: M V
authors.initials: MV
authors.lastname: Berridge
mesh_terms: D019325:3-O-Methylglucose / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D007377:Interleukin-3 / Q000502:physiology*; D007529:Isoflavones / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D047428:Protein Kinase Inhibitors; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D019311:Staurosporine / Q000494:pharmacology; D014018:Tissue Distribution; D014638:Vanadates / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D007377:Interleukin-3; D007529:Isoflavones; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D047428:Protein Kinase Inhibitors; C495678:Slc2a1 protein, mouse; C495689:Slc2a3 protein, mouse; D019325:3-O-Methylglucose; D014638:Vanadates; D003847:Deoxyglucose; D019833:Genistein; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D019311:Staurosporine; D005947:Glucose