Abstract
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 μM, 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 μM, 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.
Footnotes
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This work was supported by a Strategic Investments Scheme of The Chinese University of Hong Kong. The provision of direct grants and a graduate studentship from The Chinese University of Hong Kong is also acknowledged.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.106.111526.
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ABBREVIATIONS: DM, diabetes mellitus; SGLTs, Na+-glucose cotransporters; GLUTs, facilitative glucose transporters; STZ, streptozotocin; OGTT, oral glucose tolerance test; PEG 400, polyethylene glycol 400; T-1095, 3-(benzo[b]furan-5-yl)-2′,6′-dihydroxy-4′-methylpropiophenone 2′-O-(6-O-methoxycarbonyl-β-d-glycopyranoside).
- Received July 25, 2006.
- Accepted October 10, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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