title: Flavonoid inhibition of sodium-dependent vitamin C transporter 1 (SVCT1) and glucose transporter isoform 2 (GLUT2), intestinal transporters for vitamin C and Glucose.
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.
authors.affiliation: Molecular and Clinical Nutrition Section, Digestive Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1372, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.forename: Oran
authors.initials: O
authors.lastname: Kwon
authors.forename: Shenglin
authors.initials: S
authors.lastname: Chen
authors.forename: Rushad
authors.initials: R
authors.lastname: Daruwala
authors.forename: Peter
authors.initials: P
authors.lastname: Eck
authors.forename: Jae B
authors.initials: JB
authors.lastname: Park
authors.forename: Mark
authors.initials: M
authors.lastname: Levine
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003847:Deoxyglucose / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D017930:Genes, Reporter; D005947:Glucose / Q000378:metabolism*; D051273:Glucose Transporter Type 2; D007408:Intestinal Absorption; D007700:Kinetics; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D009865:Oocytes / Q000502:physiology; D029363:Organic Anion Transporters, Sodium-Dependent; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D012964:Sodium / Q000494:pharmacology*; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D014162:Transfection; D014982:Xenopus laevis
chemical_list: D005419:Flavonoids; D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D011506:Proteins; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D003847:Deoxyglucose; D011794:Quercetin; D012964:Sodium; D005947:Glucose; D001205:Ascorbic Acid