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Quercetin glucosides inhibit glucose uptake into brush-border-membrane vesicles of porcine jejunum

Published online by Cambridge University Press:  09 March 2007

Rainer Cermak ,
Sandra Landgraf  and
Siegfried Wolffram
Rainer Cermak
Affiliation:
Institute of Animal Nutrition, Physiology and Metabolism, Christian-Albrechts-University Kiel, Olshausenstrasse 40, D-24098 Kiel, Germany
Sandra Landgraf
Affiliation:
Institute of Animal Nutrition, Physiology and Metabolism, Christian-Albrechts-University Kiel, Olshausenstrasse 40, D-24098 Kiel, Germany
Siegfried Wolffram*
Affiliation:
Institute of Animal Nutrition, Physiology and Metabolism, Christian-Albrechts-University Kiel, Olshausenstrasse 40, D-24098 Kiel, Germany
*
*Corresponding author: Professor Dr S. Wolffram, fax +49 431 880 1528, email [email protected]
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Abstract

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Recent experimental data point to an interaction of dietary flavonol monoglucosides with the intestinal Na-dependent glucose transporter 1 (SGLT1). To investigate this interaction in more detail, we performed experiments with SGLT1-containing brush-border-membrane vesicles (BBMV) from pig jejunum. The flavonol quercetin-3-O-glucoside (Q3G) concentration-dependently inhibited Na-dependent uptake of radioactively labelled d-glucose into BBMV. Uptake of l-leucine was not inhibited by Q3G, indicating a specific interaction of the glucoside with SGLT1. Whereas the maximal transport rate of concentration-dependent initial glucose uptake was not altered in the presence of Q3G, the constant for half-maximal glucose uptake was increased, suggesting a competitive type of inhibition of glucose uptake by Q3G. Trans-stimulation experiments suggested the transport of Q3G via SGLT1. In addition, Q3G decreased the Na-independent diffusive uptake of glucose into BBMV. Other flavonoids were also tested for their inhibitory effect on d-glucose uptake. Among the tested quercetin glycosides, only the 4′-O-glucoside (Q4G) also inhibited Na-dependent glucose uptake into BBMV, whereas the 3-O-galactoside, the 3-O-glucorhamnoside and the aglycone quercetin itself were ineffective. Glucosides of some other flavonoid classes such as naringenin-7-O-glucoside, genistein-7-O-glucoside and cyanidin-3,5-O-diglucoside were ineffective as well. Thus, dietary quercetin monoglucosides, for example, Q3G and Q4G, have an impact on intestinal nutrient transporters such as SGLT1 and related systems.

Keywords

FlavonoidsQuercetin monoglucosidesIntestinal glucose transportSodium-dependent glucose transporter 1
Type
Research Article
Information
British Journal of Nutrition , Volume 91 , Issue 6 , June 2004 , pp. 849 - 855
Copyright
Copyright © The Nutrition Society 2004

References

Ader, P, Blöck, M, Pietzsch, S & Wolffram, S (2001) Interaction of quercetin glucosides with the intestinal sodium/glucose co-transporter (SGLT-1). Cancer Lett 162, 175–180.CrossRefGoogle ScholarPubMed
Ader, P, Wessmann, S & Wolffram, S (2000) Bioavailability and metabolism of the flavonol quercetin in the pig. Free Radic Biol Med 28, 1056–1067.CrossRefGoogle ScholarPubMed
Cermak, R, Landgraf, S & Wolffram, S (2003) The bioavailability of quercetin in pigs depends on the glycoside moiety and on dietary factors. J Nutr 133, 2802–2807.CrossRefGoogle ScholarPubMed
Crespy, V, Morand, C, Besson, C, Manach, C, Demigné, C & Rémésy, C (2001) Comparison of the intestinal absorption of quercetin, phloretin and their glucosides in rats. J Nutr 131, 2109–2114.CrossRefGoogle ScholarPubMed
Day, AJ, Cañada, FJ, Díaz, JC, Kroon, PA, Mclauchlan, R, Faulds, CB, Plumb, GW, Morgan, MR & Williamson, G (2000) Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett 468, 166–170.CrossRefGoogle ScholarPubMed
Day, AJ, Dupont, MS, Ridley, S, Rhodes, M, Rhodes, MJ, Morgan, MR & Williamson, G (1998) Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver beta-glucosidase activity. FEBS Lett 436, 71–75.CrossRefGoogle ScholarPubMed
Day, AJ, Gee, JM, Dupont, MS, Johnson, IT & Williamson, G (2003) Absorption of quercetin-3-glucoside and quercetin-4'-glucoside in the rat small intestine: the role of lactase phlorizin hydrolase and the sodium-dependent glucose transporter. Biochem Pharmacol 65, 1199–1206.CrossRefGoogle ScholarPubMed
de Vries, JHM, Janssen, PL, Hollman, PCH, Van Staveren, WA & Katan, MB (1997) Consumption of quercetin nd kaempferol in free-living subjects eating a variety of diets. Cancer Lett 114, 141–144.CrossRefGoogle Scholar
Gee, JM, Dupont, MS, Day, AJ, Plumb, GW, Williamson, G & Johnson, IT (2000) Intestinal transport of quercetin glycosides in rats involves both deglycosylation and interaction with the hexose transport pathway. J Nutr 130, 2765–2771.CrossRefGoogle ScholarPubMed
Gee, JM, Dupont, MS, Rhodes, MJC & Johnson, IT (1998) Quercetin glucosides interact with the intestinal glucose transport pathway. Free Radic Biol Med 25, 19–25.CrossRefGoogle ScholarPubMed
Halaihel, N, Gerbaud, D, Vasseur, M & Alvarado, F (1999) Heterogeneity of pig intestinal D-glucose transport systems. Am J Physiol 277, C1130–C1141.CrossRefGoogle ScholarPubMed
Herrmann, K (1988) On the occurence of flavonol and flavone glycosides in vegetables. Z Lebensm Unters Forsch 186, 1–5.CrossRefGoogle Scholar
Hertog, MGL, Feskens, EJ, Hollman, PCH, Katan, MB & Kromhout, D (1993 a) Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 342, 1007–1011.CrossRefGoogle ScholarPubMed
Hertog, MGL, Hollman, PCH, Katan, MB & Kromhout, D (1993 b) Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. Nutr Cancer 20, 21–29.CrossRefGoogle ScholarPubMed
Hollman, PCH, Bijsman, MNCP, Van Gameren, Y, Cnossen, EPJ, de Vries, JHM & Katan, MB (1999) The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radic Res 31, 569–573.CrossRefGoogle Scholar
Ioku, K, Pongpiriyadacha, Y, Konishi, Y, Takei, Y, Nakatani, N & Terao, J (1998) β-Glucosidase activity in the rat small intestine toward quercetin monoglucosides. Biosci Biotechnol Biochem 62, 1428–1431.CrossRefGoogle ScholarPubMed
Kessler, M, Tannenbaum, V & Tannenbaum, C (1978) A simple apparatus for performing short-time (1–2 seconds) uptake measurements in small volumes; its application to D-glucose transport studies in brush border vesicles from rabbit jejunum and ileum. Biochim Biophys Acta 509, 348–359.CrossRefGoogle ScholarPubMed
Kimmich, GA & Randles, J (1978) Phloretin-like action of bioflavonoids on sugar accumulation capability of isolated intestinal cells. Membr Biochem 1, 221–237.CrossRefGoogle ScholarPubMed
Kühnau, J (1976) The flavonoids. A class of semi-essential food components: their role in human nutrition. World Rev Nutr Diet 24, 117–191.CrossRefGoogle ScholarPubMed
Middleton, E, Kandaswami, C & Theoharides, TC (2000) The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 52 673–751.Google ScholarPubMed
Price, KR & Rhodes, MJC (1997) Analysis of the major flavonol glycosides present in four varieties of onion ( Allium cepa ) and changes in composition resulting from autolysis. J Sci Food Agric 74, 331–339.3.0.CO;2-C>CrossRefGoogle Scholar
Rimm, EB, Katan, MB, Ascherio, A, Stampfer, MJ & Willett, WC (1996) Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Ann Intern Med 125, 384–389.CrossRefGoogle ScholarPubMed
Saija, A, Scalese, M, Lanza, M, Marzullo, D, Bonina, F & Castelli, F (1995) Flavonoids as antioxidant agents: importance of their interaction with biomembranes. Free Radic Biol Med 19, 481–486.CrossRefGoogle ScholarPubMed
Sesink, ALA, Arts, ICW, Faassen-Peters, M & Hollman, PCH (2003) Intestinal uptake of quercetin-3-glucoside in rats involves hydrolysis by lactase phlorizin hydrolase. J Nutr 133, 773–776.CrossRefGoogle ScholarPubMed
Song, J, Kwon, O, Chen, S, Daruwala, R, Eck, P, Park, JB & Levine, M (2002) Flavonoid inhibition of sodium-dependent vitamin C transporter 1 (SVCT1) and glucose transporter isoform 2 (GLUT2), intestinal transporters for vitamin C and glucose. J Biol Chem 277, 15252–15260.CrossRefGoogle ScholarPubMed
Walgren, RA, Karnaky, KJ, Lindenmayer, GE & Walle, T (2000 a) Efflux of dietary flavonoid quercetin 4'-β-glucoside across human intestinal Caco-2 cell monolayers by apical multidrug resistance-associated protein-2. J Pharmacol Exp Ther 294, 830–836.Google Scholar
Walgren, RA, Lin, JT, Kinne, RKH & Walle, T (2000 b) Cellular uptake of dietary flavonoid quercetin 4'-β-glucoside by sodium-dependent glucose transporter SGLT1. J Pharmacol Exp Ther 294, 837–843.Google Scholar
Walle, T & Walle, UK (2003) The β-D-glucoside and sodium-dependent glucose transporter 1 (SGLT1)-inhibitor phloridzin is transported by both SGLT1 and multidrug resistance-associated proteins 1/2. Drug Metab Dispos 31, 1288–1291.CrossRefGoogle ScholarPubMed
Wilbrandt, W & Rosenberg, T (1961) The concept of carrier transport and its corollaries in pharmacology. Pharmacol Rev 13, 109–183.Google ScholarPubMed
Wolffram, S, Blöck, M & Ader, P (2002) Quercetin-3-glucoside is transported by the glucose carrier SGLT1 across the brush border membrane of rat small intestine. J Nutr 132, 630–635.CrossRefGoogle ScholarPubMed
Wolffram, S, Hagemann, C, Grenacher, B & Scharrer, E (1992) Characterization of the transport of tri- and dicarboxylates by pig intestinal brush-border membrane vesicles. Comp Biochem Physiol 101, 759–767.CrossRefGoogle ScholarPubMed