Inhibition of the intestinal glucose transporter GLUT2 by flavonoids

• Published in: The FASEB journal Vol. 21; no. 2; pp. 366 - 377
• Main Authors: Kwon, Oran, Eck, Peter, Chen, Shenglin, Corpe, Christopher P, Lee, Je-Hyuk, Kruhlak, Michael, Levine, Mark
• Format: Journal Article
• Language: English
• Published: United States The Federation of American Societies for Experimental Biology 01.02.2007
• Subjects: Animals; Biological Transport - drug effects; Caco-2 Cells; Cell Line, Tumor; Female; Flavonoids - chemistry; Flavonoids - pharmacology; Fructose - metabolism; Glucose - metabolism; Glucose Transporter Type 2 - genetics; Glucose Transporter Type 2 - physiology; Glucose Transporter Type 5 - physiology; Humans; Intestines - metabolism; Mice; Microscopy, Confocal; Models, Biological; Molecular Structure; Oocytes - drug effects; Oocytes - metabolism; Quercetin - chemistry; Quercetin - pharmacology; Sodium-Glucose Transporter 1 - genetics; Sodium-Glucose Transporter 1 - physiology; Xenopus laevis
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.06-6620com

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 isoquercetrin. IC₅₀s for quercetin, myricetin, and isoquercetirin were ~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.--Kwon, O., Eck, P., Chen, S., Corpe, C. P., Lee, J-H., Kruhlak, M., Levine, M. Inhibition of the intestinal glucose transporter GLUT2 by flavonoids.