Abstract
This work investigates the effects of dietary polyphenols on intestinal glucose transport and gastrointestinal hormone secretion using an in vitro cell culture model, an in vivo rodent model and in vivo studies in healthy volunteers. Glucose uptake was inhibited in Caco-2 cells under sodium-dependent conditions (favouring active transport) by the glycosides and the non-glycosylated dietary polyphenols whereas the aglycones and the phenolic acids had no significant effects. Under sodium-free conditions (favouring facilitated transport), the aglycones and the non-glycosylated dietary polyphenols showed the greatest effects, whereas the glycosides and the phenolic acids had no significant effects. This suggests that the aglycones inhibit facilitated glucose uptake whereas the glycosides inhibit the active transport of glucose. The non-glycosylated dietary polyphenols were effective under both sets of conditions and appear to exert their effects via steric hindrance. Intragastric gavage studies in rodents using a standard oral dose of glucose (3. 2 g/kg body weight) showed a reduction in blood glucose concentrations over the first 10 minutes of the time course when administered with quercetin-3-glucoside (P<0. 05) and quercetin-4’glucoside (P<0. 10) (present at 1/50 molar concentration of glucose). These effects were transient since the inhibition was lost by 20 minutes. No effects were observed on plasma insulin, glucose-dependent insulinotropic-polypeptide (GIP) or glucagon-like peptide-1 (GLP-1) concentrations due to late blood sampling. These results suggest that quercetin glucosides interact with glucose transport proteins in the small intestine. Studies in human volunteers showed that the absorption of 25 g of glucose, and the secretion of insulin, GIP and GLP-1 were significantly altered when administered with a polyphenol-rich food. Apple juice consumption significantly reduced plasma glucose, insulin, and GIP concentrations and increased plasma GLP-1 concentrations which is consistent with a delay in the upper intestinal uptake of glucose. Consumption of the glucose in an instant coffee drink showed a reduction in plasma GIP and an increase in plasma GLP-1 concentrations, observations again consistent with a delay in glucose absorption. Iso-genic onions with high and low flavonoid contents caused a significant reduction in plasma glucose, insulin and GIP concentrations when compared with the control which is attributable to the high dietary fibre content. However, a larger reduction was observed after consumption of the high-flavonoid onions compared with the low-flavonoid onions suggesting a role for the quercetin glucosides. No effects on plasma GLP-1 concentrations were observed. Taken together, these data indicate that dietary polyphenols exert the ability to inhibit intestinal glucose uptake in vitro and in vivo and suggests a possible role for these compounds as antihyperglycaemic agents.