Puerarin and daidzin are the major isoflavone glucosides found in kudzu dietary supplements. In thisstudy, we demonstrated that puerarin significantly improves glucose tolerance in C57BL/6J-ob/obmice, an animal model of type 2 diabetes mellitus, blunting the rise in blood glucose levels after i.p.administration of glucose. In contrast, daidzin, the O-glucoside, had a significant but opposite effect,impairing glucose tolerance as compared to saline-treated controls. When they were administeredi.p. with
14C-glucose to C57BL/6J lean mice, puerarin inhibited glucose uptake into tissues andincorporation into glycogen, while daidzin stimulated glucose uptake, showing an opposite effect topuerarin. Puerarin also antagonized the stimulatory effect of decyl-
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D-thiomaltoside, an artificial primerof glycogen synthesis, which increases
14C-glucose uptake and incorporation into glycogen in mouseliver and heart. A liquid chromatography-tandem mass spectrometry procedure was used toinvestigate the metabolism and bioavailability of puerarin and daidzin. The blood puerarin concentration-time curve by i.p. and oral administration indicated that puerarin was four times more bioavailablevia i.p. injection than via the oral route of administration. This may account for the increasedhypoglycemic effect seen in the i.p. glucose tolerance test vs that seen orally. Our results suggestthat puerarin is rapidly absorbed from the intestine without metabolism, while daidzin is hydrolyzedto the aglycone daidzein. The opposing effects of puerarin and daidzin on glucose homeostasis mayhave implications for the activity of dietary supplements that contain both of these isoflavonoids.Keywords: Glucose tolerance test; puerarin; daidzin, kudzu; metabolism; LC-MS-MS