Regulation of hexose transport in aortic endothelial cells by vascular permeability factor and tumor necrosis factor-alpha, but not by insulin

Vascular permeability factor (VPF) is mitogenic for bovine aortic endothelial (BAE) cells, whereas tumor necrosis factor (TNF) is cytostatic and was found to completely block the mitogenic response to VPF. In contrast to the apparently antagonistic mitogenic effects that these two factors elicit, chronic exposure of BAE cells to either VPF of TNF resulted in significant (about 3-fold) increases in the rates of hexose transport. The concentrations required for half-maximal stimulation were 2 ng/ml (40 pM) for TNF and 4 ng/ml (100 pM) for VPF. Exposure to both factors simultaneously resulted in a greater stimulation of transport (about 7-fold) than exposure to either factor alone. Northern blot analysis indicated that the amount of message for the GLUT-1/erythrocyte form of the glucose transporter was specifically increased by treatment with VPF (5-fold), TNF (25-fold), or to both cytokines together (35-fold). Expression of mRNAs for the insulin-sensitive muscle/adipose transporter (GLUT-4), brain/fetal skeletal muscle transporter (GLUT-3), or the hepatic transporter (GLUT-2) were not detected in either control or treated cells. Acute or chronic exposure to insulin (10(-9) to 10(-6) M) did not activate hexose transport in BAE cells. Thus, glucose transport in aortic endothelial cells can be up-regulated by either VPF, a growth stimulator, or by TNF, a growth inhibitor, but not by insulin. The additive effect of the two cytokines together may be important in the control of increased glucose metabolism at sites of inflammation.