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  • Title: Cellular uptake of dietary flavonoid quercetin 4'-beta-glucoside by sodium-dependent glucose transporter SGLT1.
    Author: Walgren RA, Lin JT, Kinne RK, Walle T.
    Journal: J Pharmacol Exp Ther; 2000 Sep; 294(3):837-43. PubMed ID: 10945831.
    Abstract:
    Although it has been suggested that the intestinal glucose transporter may actively absorb dietary flavonoid glucosides, there is a lack of direct evidence for their transport by this system. In fact, our previous studies with the human Caco-2 cell model of intestinal absorption demonstrated that a major dietary flavonoid, quercetin 4'-beta-glucoside, is effluxed by apically expressed multidrug resistance-associated protein-2, potentially masking evidence for active absorption. The objective of this study was to test the hypothesis that quercetin 4'-beta-glucoside is a substrate for the intestinal sodium-dependent D-glucose cotransporter SGLT1. Cellular uptake of quercetin 4'-beta-glucoside was examined with Caco-2 cells and SGLT1 stably transfected Chinese hamster ovary cells (G6D3 cells). Although quercetin 4'-beta-glucoside is not absorbed across Caco-2 cell monolayers, examination of the cells by indirect fluorescent microscopy as well as by HPLC analysis of cellular content revealed cellular accumulation of this glucoside after apical loading. Consistent with previous observations, the accumulation of quercetin 4'-beta-glucoside in both Caco-2 and G6D3 cells was markedly enhanced in the presence of multidrug resistance-associated protein inhibition. Uptake of quercetin 4'-beta-glucoside was greater in SGLT1-transfected cells than in parental Chinese hamster ovary cells. Uptake of the glucoside by Caco-2 and G6D3 cells was sodium-dependent and was inhibited by the monovalent ionophore nystatin. In both Caco-2 and G6D3 cells, quercetin 4'-beta-glucoside uptake was inhibited by 30 mM glucose and 0.5 mM phloridzin. These results demonstrate for the first time that quercetin 4'-beta-glucoside is transported by SGLT1 across the apical membrane of enterocytes.
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