Glucose modulates vitamin C transport in adult human small intestinal brush border membrane vesicles

The uptake of L-ascorbate (vitamin C) and its oxidized form, dehydro-L-asco rbic acid (DHAA), was evaluated in brush border membrane vesicles isolated from adult human duodenum, jejunum and ileum, Ascorbate was taken up along the entire length of the small intestine with a threefold higher initial up take rate in distal than proximal segments. Ascorbate uptake was Nai-depend ent, potential-sensitive and saturable (K-m, 200 mu mol/L), whereas DHAA tr ansport involved facilitated diffusion (K-m, 800 mu mol/L). Pharmacologic e xperiments were conducted to characterize further these transport mechanism s. DHAA uptake was not mediated by the fructose carrier GLUT5, the uridine transporter or the 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)- sensitive anion exchanger of the apical membrane. DIDS and sulfinpyrazone, an inhibitor of the urate/lactate exchanger, both significantly reduced the initial rate of ascorbate uptake. Acidic pH inhibited ascorbate uptake, an d this effect was not due to a transmembrane proton gradient. Increasing co ncentrations of glucose in the transport media also significantly inhibited ascorbate uptake, but no effect of glucose was seen when glucose internali zation was blocked by phlorizin, Preloading the vesicles with glucose inhib ited ascorbate uptake similarly, indicating that glucose interferes with th e ascorbate transporter from the internal side of the membrane. The results of this study suggest that DHAA crosses the apical membrane by facilitated diffusion, whereas ascorbate transport is a Na+-dependent, electrogenic pr ocess modulated by glucose.