title: Inhibition of the intestinal glucose transporter GLUT2 by flavonoids.
abstract: We tested whether the dominant intestinal sugar transporter GLUT2 was inhibited by intestinal luminal compounds that are inefficiently absorbed and naturally present in foods. Because of their abundance in fruits and vegetables, flavonoids were selected as model compounds. Robust inhibition of glucose and fructose transport by GLUT2 expressed in Xenopus laevis oocytes was produced by the flavonols myricetin, fisetin, the widely consumed flavonoid quercetin, and its glucoside precursor isoquercitrin [corrected]. IC50s for quercetin, myricetin, and isoquercitirin [corrected]were approximately 200- to 1000-fold less than glucose or fructose concentrations, and noncompetitive inhibition was observed. The two other major intestinal sugar transporters, GLUT5 and SGLT1, were unaffected by flavonoids. Sugar transport by GLUT2 overexpressed in pituitary cells and naturally present in Caco-2E intestinal cells was similarly inhibited by quercetin. GLUT2 was detected on the apical side of Caco-2E cells, indicating that GLUT2 was in the correct orientation to be inhibited by luminal compounds. Quercetin itself was not transported by the three major intestinal glucose transporters. Because the flavonoid quercetin, a food component with an excellent pharmacology safety profile, might act as a potent luminal inhibitor of sugar absorption independent of its own transport, flavonols show promise as new pharmacologic agents in the obesity epidemic.
authors.affiliation: Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Oran
authors.initials: O
authors.lastname: Kwon
authors.forename: Peter
authors.initials: P
authors.lastname: Eck
authors.forename: Shenglin
authors.initials: S
authors.lastname: Chen
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Corpe
authors.forename: Je-Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Kruhlak
authors.forename: Mark
authors.initials: M
authors.lastname: Levine
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D044948:Flavonols; D005632:Fructose / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000502:physiology*; D051296:Glucose Transporter Type 5 / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D008954:Models, Biological; D015394:Molecular Structure; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D005419:Flavonoids; D044948:Flavonols; D051273:Glucose Transporter Type 2; D051296:Glucose Transporter Type 5; D051269:Sodium-Glucose Transporter 1; D005632:Fructose; C040015:myricetin; D011794:Quercetin; D005947:Glucose; C017875:fisetin