Intestinal Dehydroascorbic acid (DHA) transport mediated by the facilitative sugar transporters, GLUT2 and GLUT8

Intestinal vitamin C (ascorbate) absorption was believed to be mediated by the Na+ dependent ascorbic acid transporter, SVCT1. However, ascorbate transport across intestines of SVCT1 knockout mice is normal indicating that alternative ascorbic acid transport mechanisms exist. To investigate these mechanisms, rodents were gavaged with ascorbate or its oxidized form dehydroascorbic acid (DHA), and plasma ascorbate concentrations measured. Ascorbate concentrations doubled following DHA but not ascorbate gavage. We hypothesized that the transporters responsible were facilitated glucose transporters (GLUTs). Using xenopus oocyte expression, we investigated whether facilitative glucose transporters GLUT2, and GLUT5-12 transported DHA. Only GLUT2 and GLUT8, known to be expressed in intestines, transported DHA with apparent transport affinities (Km) of 2.33 and 3.23 mM, and maximal transport rates (Vmax) of 25.9 and 10.1 pmols/mins/ oocyte, respectively. Maximal rates for DHA transport mediated by GLUT2 and GLUT8 in oocytes were lower than maximal rates for 2-DG (Vmax of 224 and 32 pmoles/min/oocyte for GLUT2 and GLUT8, respectively) and fructose (Vmax of 406 and 116 pmols/min/oocyte for GLUT2 and GLUT8, respectively). These findings may be explained by differences in the exofacial binding of substrates, as shown by inhibition studies with ethylidine glucose. DHA transport activity in GLUT2 and GLUT8 expressing oocytes were inhibited by glucose, fructose, and by the flavonoids phloretin and quercetin. These studies indicate intestinal DHA transport may be mediated by the facilitative sugar transporters, GLUT2 and GLUT8. Furthermore, dietary sugars and flavonoids in fruits and vegetables may module ascorbate bioavailability via inhibition of small intestinal GLUT2 and GLUT8.