Rhubarb extracts have been reported to improve oral
glucose tolerance in diabetic animals. In the present study we have investigated the
antidiabetic actions of
desoxyrhaponticin, a major
stilbene in rhubarb, as a
glucose uptake inhibitor.
Desoxyrhaponticin was demonstrated to inhibit
glucose uptake in rabbit intestinal membrane vesicles as well as in rat everted gut sleeves, with IC50 values of 148.3 and 30.9 microM, respectively. Kinetics studies revealed that
desoxyrhaponticin is a competitive inhibitor of
glucose uptake in both systems. Moreover,
desoxyrhaponticin could reduce
glucose uptake in the intestinal membrane vesicles of both normal and diabetic rats. In addition,
glucose uptake in the renal membrane vesicles of both normal and diabetic rats was reduced by
desoxyrhaponticin. Under the inhibition of
desoxyrhaponticin, uptake of
glucose in both the intestinal and renal membrane vesicles of the normal rats was no different from that of the diabetic rats. The IC50 values of the uptake inhibition in the renal membrane vesicles of normal and diabetic rats were 118.8 and 115.7 microM, respectively. In a type 2 diabetic animal model in which rats have been treated with
streptozotocin at the neonatal stage,
postprandial hyperglycemia was significantly suppressed by
oral administration of this compound (300 mg/kg b.wt.). These results suggest that
desoxyrhaponticin is an agent that is potentially effective in controlling
postprandial hyperglycemia in diabetes. The in vivo
antidiabetic action of this compound can be explained, in part at least, by inhibition of
glucose transport in the small intestine and inhibition of
glucose reabsorption in the kidney.