Identification of a sorbitol permease in human erythrocytes.

Sorbitol, a polyol derived from glucose by the enzyme, aldose reductase, is a common organic solute in many cells. It plays a role in the osmotic regulation of epithelial cells and in the pathology of uncontrolled diabetes. To learn more about sorbitol transport, we measured D-[14C]sorbitol influx in human erythrocytes. Sorbitol influx at 37 degrees C was a linear function of sorbitol concentration over the range of 0.05-100 mM. The activation energy for sorbitol influx was 10.0 kcal/mol, and the Q10 over the range 10-50 degrees C was 1.8, higher than predicted for diffusion through an aqueous pore. Glucose transport inhibitors either had no effect (1 mM phloridzin) or minimally inhibited (approximately 35% inhibition by 10 microM cytochalasin B or 250 microM phloretin) sorbitol influx. Influx was stimulated twofold by 0.5 mM p-chloromercuribenzoic acid, an inhibitor of glucose transport, and this was reversed by 2 mM dithiothreitol. Sorbitol influx was neither Na dependent nor sensitive to changes in cell volume. Glucose, fructose, mannitol, myo-inositol, and gluconate, at four- to fivefold molar excesses over sorbitol, did not inhibit its influx. We conclude that there is a specific sorbitol transport pathway in human erythrocytes similar to the sorbitol permease in renal epithelial cells.