Effect of Polyphenols on Sugar Transport by GLUT2, GLUT5 and GLUT7
Authors: Gauer Julia , Tumova Sarka , Gardner Samantha , Kerimi Asimina , Lippiat Jonathan , McKeown Lynn , Williamson Gary 
Published: November 2023

BackgroundHigh 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. For instance, some authors have claimed that excess intake of fructose can promote hyperinsulinemia, hyperglycemia, hepatic insulin resistance, as well as increased serum LDL‐cholesterol and triglycerides in humans. We hypothesized that plant‐derived compounds, (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 fructoseAimDetermine the direct impact of specific (poly)phenols and food extracts on glucose uptake by GLUT2 and GLUT7 transporters, as well as their effect on sugar uptake by the fructose specific transporter GLUT5.MethodsXenopus laevis oocytes were injected with the relevant transporter cRNA. After protein expression, oocytes were incubated in a 14C‐glucose/fructose solution containing individual (poly)phenols and extracts. Automated capillary PorteinSimple Western blotting confirmed protein expression on oocyte membranes and uptake of internalized 14C‐glucose/fructose was observed by liquid scintillation counting. The caco‐2/TC7 cell model was additionally used to further investigate GLUT7 expression.ResultsUptake of 14C‐fructose by GLUT5 was significantly inhibited by L‐sorbose‐Bn‐OZO, as expected. In addition, German chamomile (Matricaria recucita) extract (IC50 = 0.73±0.18 mg/ml), hesperidin (IC50 = 264±72 μM) and hesperetin (32.7 % inhibition at 500 μM) inhibited fructose uptake by GLUT5; these inhibition values are relevant only for the gut lumen. 14C‐glucose uptake by GLUT2 was significantly inhibited by phloretin, cytochalasin B and quercetin. Significant dose dependent inhibition of GLUT2 was achieved by German chamomile (IC50 = 0.49±0.24 mg/ml), green tea (IC50 = 0.13±0.02 mg/ml) and sugar‐free pomegranate (93 % reduction at 0.1 mg/ml) extracts, in addition to pure compounds EGCG (IC50 = 177±44 μM), apigenin (IC50 = 24±4 μM), hesperidin (IC50 = 219±40 μM) and hesperetin (82.9 % at 50 μM). 14C‐glucose uptake by GLUT7 was not inhibited by phloretin, cytochalasin B nor by any extract or pure compound tested. 14C‐glucose uptake by GLUT7 is significantly decreased by fructose, most likely due to competitive inhibition. Fructose (25 mM for 3 wk) induced GLUT7 protein and mRNA in Caco‐2/TC7 cells.ConclusionGerman chamomile extract, hesperetin and hesperidin inhibited fructose uptake by GLUT5 and glucose uptake by GLUT2. 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.Support or Funding InformationSupported by the European Research Council Advanced Grant POLYTRUE? (322467)Acknowledgement: GLUT5 inhibitor, L‐sorbose‐Bn‐OZO, kindly supplied by Prof. Arnaud Tatibouet, Université d'Orléans, Orléans, France. The Caco2/TC7 cell line was a kind gift by Prof. Monique Rousset, Centre de Recherche des Cordeliers, Paris, France.