Effects of cadmium on glucose transport in rat adipocytes and human erythrocytes: stimulation of GLUT1 catalytic activity

Abstract

The effects of cadmium on facilitative glucose transporter function In rat adipocytes were studied. A short (30 min) incubation with cadmium resulted in stimulation of 3-O-methyl-D-glucose (3OMG ) equilibrium exchange in rat adipocytes as much as four-fold. The stimulation was a saturable function of cadmium concentation with the half-maximal effect at approximately 0.5 mM CdS04. The stimulation was due to an increase in Vmax with no significant changes in KM. No further stimulation of 30MG flux was observed once adipocytes were maximally stimulated by insulin. Semiquantitative immunoblot analysis of subcellular fractions revealed that the stimulation was accompanied by an insignificant and only a modest (less than 50%) increase in plasma membrane GLUT4 and GLUT1 levels, respectively, suggesting that the stimulation involves largely an increased catalytic activity of either or both of GLUTI and GLUT4. We next studied effect of cadmium on GLUT1 selectively using human erythrocytes and purified GLUT1 reconstituted in liposomes. With purified GLUTI, cadmium inhibited cytochalasin B binding and stimulated 30MG flux, indicating that cadmium directly interacts with GLUTI. Cadmium, however, did not affect the 30MG flux in intact human erythrocytes or their resealed ghosts. These findings strongly suggest that cadmium stimulates the catalytic activity of GLUT1 and GLUT4 in adipocytes, and this effect is suppressed by a cell-specific factor or factors in human erythrocytes.