Abstract
Vitamin C and flavonoids, polyphenols with uncertain function, are abundant in fruits and vegetables. We postulated that flavonoids have a novel regulatory action of delaying or inhibiting absorption of vitamin C and glucose, which are structurally similar. From six structural classes of flavonoids, at least 12 compounds were chosen for studies. We investigated the effects of selected flavonoids on the intestinal vitamin C transporter SVCT1(h) by transfecting and overexpressing SVCT1(h) in Chinese hamster ovary cells. Flavonoids reversibly inhibited vitamin C transport in transfected cells with IC(50) values of 10-50 microm, concentrations expected to have physiologic consequences. The most potent inhibitor class was flavonols, of which quercetin is most abundant in foods. Because Chinese hamster ovary cells have endogenous vitamin C transport, we expressed SVCT1(h) in Xenopus laevis oocytes to study the mechanism of transport inhibition. Quercetin was a reversible and non-competitive inhibitor of ascorbate transport; K(i) 17.8 microm. Quercetin was a potent non-competitive inhibitor of GLUT2 expressed in Xenopus oocytes; K(i) 22.8 microm. When diabetic rats were administered glucose with quercetin, hyperglycemia was significantly decreased compared with administration of glucose alone. Quercetin also significantly decreased ascorbate absorption in normal rats given ascorbate plus quercetin compared with rats given ascorbate alone. Quercetin was a specific transport inhibitor, because it did not inhibit intestinal sugar transporters GLUT5 and SGLT1 that were injected and expressed in Xenopus oocytes. Quercetin inhibited but was not transported by SVCT1(h). Considered together, these data show that flavonoids modulate vitamin C and glucose transport by their respective intestinal transporters and suggest a new function for flavonoids.
Highlights
Flavonoids are polyphenols that are widely distributed in plant foods and ingested by humans
Inhibition of glucose transport by genistein was competitive and occurred in cells overexpressing GLUT1.1 In other experiments several flavonoid classes inhibited transport of glucose, dehydroascorbic acid, and ascorbate in three leukemic cell types, the most potent inhibition occurring with flavonols, and the effects could not be explained by ascorbate oxidation [10, 11]
Compared with vector-alone-transfected cells, ascorbate transport increased 5– 6-fold over 15 min in cells stably transfected with SVCT1(h) (Fig. 1A)
Summary
Vol 277, No 18, Issue of May 3, pp. 15252–15260, 2002 Printed in U.S.A. Flavonoid Inhibition of Sodium-dependent Vitamin C Transporter 1 (SVCT1) and Glucose Transporter Isoform 2 (GLUT2), Intestinal Transporters for Vitamin C and Glucose*. Inhibition of glucose transport by genistein was competitive and occurred in cells overexpressing GLUT1.1 In other experiments several flavonoid classes inhibited transport of glucose, dehydroascorbic acid, and ascorbate in three leukemic cell types, the most potent inhibition occurring with flavonols, and the effects could not be explained by ascorbate oxidation [10, 11]. Ascorbate transport is sodium-dependent and is mediated by ascorbate transporters SVCT1 and SVCT2, neither of which transport glucose and dehydroascorbic acid [22, 23] By coupling these transport mechanisms and the observations that flavonoids inhibited several distinct cellular transport activities, new insights into flavonoid function become possible. The data indicate that flavonols, a flavonoid class abundant in plant foods consumed by humans, are potent noncompetitive and reversible inhibitors of SVCT1(h) and GLUT2 at concentrations predicted from dietary ingestion
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