Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.729469
Title: Effect of polyphenols on sugar transport by human GLUT2, GLUT5 and GLUT7
Author: Sandrin Gauer, Julia
ISNI:       0000 0004 6494 8159
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2017
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Abstract:
Background: High dietary sugar intake is controversially associated with an increase in prevalence of type 2 diabetes globally. This has been attributed to the impact that sugars have in the development of disease risk factors linked to diabetes, cardiovascular disease and others. (Poly)phenols present in our daily diet may affect these processes by multiple mechanisms, including effects on the digestion, uptake and post-prandial distribution of glucose and fructose. Aim: Study the expression of GLUT7 in Caco-2/TC7 intestinal cells and identify novel inhibitors of sugar transporters by determining the direct impact of specific (poly)phenols and extracts on fructose and glucose uptake by GLUT2 and GLUT7 transporters, as well as their effect on sugar uptake by the fructose specific transporter GLUT5. Methods: The Caco-2/TC7 cell model was used to investigate GLUT7 expression. For sugar transport studies, X. laevis oocytes were injected with the relevant transporter mRNA. After protein expression, oocytes were incubated in a 14C-glucose/fructose solution containing individual (poly)phenols and extracts. Automated capillary Western blotting (Wes) confirmed protein expression on oocyte membranes and uptake of internalysed 14C-glucose/fructose was observed by liquid scintillation counting. Results: The presence of fructose led to a significant increase in GLUT7 expression, as determined by mRNA (13% increase, p ≤ 0.001) and protein (2.7-fold increase, p ≤ 0.05) analysis of the Caco-2/TC7 cell model. GLUT5-mediated fructose transport was significantly inhibited by German chamomile extract (IC50 of 0.73±0.18 mg/ml), sugar-free pomegranate extract (0.48 ± 0.22 mg/ml), apigenin (IC50 = 40 ± 4 μM), (–)-epigallocatechin-gallate (EGCG) (IC50= 72 ± 13 μM) and hesperidin (IC50 = 264 ± 72 μM). GLUT2-mediated glucose transport was significantly inhibited by various compounds and extracts, including quercetin (IC50 = 7 ± 1 μM), EGCG (IC50 = 72 ± 13 μM) and apigenin (IC50 = 27 ± 4 μM). These three compounds also significantly inhibited fructose transport by GLUT2; IC50 = 8 ± 2 μM for quercetin, 93 ± 16 μM for EGCG and 28 ± 10 μM for apigenin. In addition, apigenin significantly decreased the uptake of both glucose (IC50 = 38 ± 2 μM) and fructose (IC50 = 16 ± 12 μM) by GLUT7. Conclusions: The quantitative model used to investigate the molecular mechanism of GLUT2, GLUT5 and GLUT7 inhibition by specific (poly)phenols, achieved through over-expression of transporters in X. laevis oocytes, identified novel inhibitors for each of these individual transporters. In addition, apigenin was shown to be a potent inhibitor of sugar transport by all three GLUTs investigated. Moreover, fructose was shown to modulate expression of GLUT7 in the Caco-2/TC7 model. Further characterisation of the lesser known GLUT7, sharing 58% sequence similarity to GLUT5, will help highlight any role it may play in regulation of sugar uptake. Overall these results suggest that some of these compounds or extracts may have potential in interventions aimed at the control of post-prandial blood sugar levels in both healthy volunteers and diabetic patients.
Supervisor: Williamson, Gary ; Mckeown, Lynn Sponsor: ERC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.729469  DOI: Not available
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