Gauer, JS orcid.org/0000-0002-0835-639X, Tumova, S orcid.org/0000-0003-2044-4998, Lippiat, JD orcid.org/0000-0003-3748-7345 et al. (2 more authors) (2018) Differential patterns of inhibition of the sugar transporters GLUT2, GLUT5 and GLUT7 by flavonoids. Biochemical Pharmacology, 152. pp. 11-20. ISSN 0006-2952
Abstract
Only limited data are available on the inhibition of the sugar transporter GLUT5 by flavonoids or other classes of bioactives. Intestinal GLUT7 is poorly characterised and no information exists concerning its inhibition. We aimed to study the expression of GLUT7 in Caco-2/TC7 intestinal cells, and evaluate inhibition of glucose transport by GLUT2 and GLUT7, and of fructose transport by GLUT2, GLUT5 and GLUT7, by flavonoids. Differentiated Caco-2/TC7 cell monolayers were used to investigate GLUT7 expression, as well as biotinylation and immunofluorescence to assess GLUT7 location. For mechanistic sugar transport studies, X. laevis oocytes were injected with individual mRNA, and GLUT protein expression on oocyte membranes was confirmed. Oocytes were incubated with D-[14C(U)]-glucose or D-[14C(U)]-fructose in the presence of flavonoids, and uptake was estimated by liquid scintilation counting. In differentiated Caco-2/TC7 cell monolayers, GLUT7 was mostly expressed apically. When applied apically, or to both compartments, sorbitol, galactose, L-glucose or sucrose did not affect GLUT7 mRNA expression. Fructose applied to both sides increased GLUT7 mRNA (13%, p ≤ 0.001) and total GLUT7 protein (2.7-fold, p ≤ 0.05), while the ratio between apical, basolateral and total GLUT7 protein was unchanged. In the X. laevis oocyte model, GLUT2-mediated glucose and fructose transport were inhibited by quercetin, (−)-epigallocatechin gallate (EGCG) and apigenin, GLUT5-mediated fructose transport was inhibited by apigenin and EGCG, but not by quercetin, and GLUT7-mediated uptake of both glucose and fructose was inhibited by apigenin, but not by quercetin nor EGCG. Expression of GLUT7 was increased by fructose, but only when applied to Caco-2/TC7 cells both apically and basolaterally. Since GLUT2, GLUT5 and GLUT7 show different patterns of inhibition by the tested flavonoids, we suggest that they have the potential to be used as investigational tools to distinguish sugar transporter activity in different biological settings.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2018 Elsevier Inc. All rights reserved. This is an author produced version of a paper published in Biochemical Pharmacology. Uploaded in accordance with the publisher's self-archiving policy |
Keywords: | Polyphenols; Xenopus laevis oocytes; Sugar transporters; Flavonoids; Caco-2 cells |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Funding Information: | Funder Grant number EU - European Union 322467 |
Depositing User: | Symplectic Publications |
Date Deposited: | 13 Mar 2018 12:35 |
Last Modified: | 14 Mar 2019 01:39 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.bcp.2018.03.011 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:128423 |
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