Inhibition of intestinal and renal Na+-glucose cotransporter by naringenin

Abstract Reduction in glucose uptake constitutes a possible means of controlling diabetic hyperglycemia. Using purified intestinal brush border membrane vesicles and everted intestinal sleeves, we have demonstrated that naringenin, a flavonoid present in citrus fruits and juices, significantly inhibited glucose uptake in the intestine. In addition, naringenin also elicited inhibitory actions towards glucose uptake in renal brush border membrane vesicles. Naringin, a glycoside of naringenin, was totally inactive in these aspects. Naringenin exhibited moderate inhibitory action on glucose uptake in rabbit intestinal brush border membrane vesicles, and showed strong inhibitory action in rat everted intestinal sleeves. The IC 50 values were 205.9 and 2.4 μmol/l, respectively. Lineweaver–Burk analysis demonstrated that naringenin inhibited glucose uptake in rat everted intestinal sleeves in a competitive manner with a K i value of 1.1 μmol/l. Glucose uptake activities in both the intestinal and renal brush border membrane vesicles of diabetic rats were significantly higher than in normal rats. Naringenin (500 μM) reduced glucose uptake by more than 60% in both the intestinal and renal brush border membrane vesicles of diabetic rats to a level similar to that of the normal rats. The IC 50 values of naringenin in the renal brush border membrane vesicles of normal and diabetic rats were 323.9 and 166.1 μmol/l, respectively. These results suggest that inhibition of intestinal glucose uptake and renal glucose reabsorption explains, in part at least, the in vivo antihyperglycemic action of naringenin and its derivatives. The possible application of these natural compounds in controlling hyperglycemia warrants further investigations.