2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)-INDUCED CHANGES IN GLUCOSETRANSPORTING ACTIVITY IN GUINEA-PIGS, MICE, AND RATS IN-VIVO AND IN-VITRO

The toxic action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gluc ose uptake was studied on different species, sexes, and strains of ani mals by using a nonmetabolizable glucose analog, 3-0-methyl D [1-H-3] glucose (H-3-Me-glc). We have found a drastic reduction in glucose upt ake in different organs from male guinea pigs in vivo as well as in vi tro. Female guinea pigs were less responsive to this effect of TCDD co mpared to males. Highly TCDD-responsive mice strains responded in the same way as the male guinea pigs, while less TCDD-responsive mice stra ins did not. A reduction in glucose uptake was found in explant adipos e tissue cultures (in vitro) of male mice (highly TCDD-responsive) aft er a 4 hour incubation with 10(-8) M TCDD. In less responsive mice str ains, stimulation was observed using the same model (in vitro). In the case of male rats, as well as male guinea pigs, glucose uptake was hi ghly reduced by 10(-8) M TCDD using an in vitro system of explant adip ose tissue. The Ah-receptor blocker, 4,7-phenanthroline, abolished the effect of TCDD on inhibition of glucose uptake in adipose tissue of m ale guinea pigs both in vivo and in vitro. Transcription and translati on inhibitors (actinomycin D and cycloheximide, respectively) were tes ted separately or in combination with TCDD using the guinea pig adipos e tissue culture model. It was found that actinomycin D could block th e effect of TCDD on glucose uptake throughout the experiment time (360 min) while cycloheximide blocked TCDD action for about 60 minutes. Pr otein kinase inhibitors (e.g., genistein, neomycin) did not change the effect of TCDD on glucose uptake in male guinea pig adipose tissue. B ased on these observations, we conclude that TCDD inhibits Me-glc upta ke in various organs in guinea pigs, mice, and rats, and this response is mediated by the Ah-receptor.