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-ascorbic 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 uptake rate in distal than proximal segments. Ascorbate uptake was Na(+)-dependent, potential-sensitive and saturable (K(m), 200 micromol/L), whereas DHAA transport involved facilitated diffusion (K(m), 800 micromol/L). Pharmacologic experiments were conducted to characterize further these transport mechanisms. 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, and this effect was not due to a transmembrane proton gradient. Increasing concentrations of glucose in the transport media also significantly inhibited ascorbate uptake, but no effect of glucose was seen when glucose internalization was blocked by phlorizin. Preloading the vesicles with glucose inhibited ascorbate uptake similarly, indicating that glucose interferes with the 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 process modulated by glucose.
Malo
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Membrane Transport Research Group, Department of Physiology, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
Wilson
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JX
D000328:Adult; D001205:Ascorbic Acid / Q000493:pharmacokinetics*; D001386:Azides / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D003683:Dehydroascorbic Acid / Q000493:pharmacokinetics; D005947:Glucose / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D008871:Microvilli / Q000187:drug effects* / Q000378:metabolism; D013861:Thiocyanates / Q000494:pharmacology; D014018:Tissue Distribution
D001386:Azides; D013861:Thiocyanates; D005947:Glucose; C031760:thiocyanate; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid