Enan E, Matsumura F
Department of Environmental Toxicology, University of California, Davis 95616.
J Biochem Toxicol. 1994 Apr;9(2):97-106. doi: 10.1002/jbt.2570090207.
The toxic action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on glucose uptake was studied on different species, sexes, and strains of animals by using a nonmetabolizable glucose analog, 3-0-methyl D [1-3H] glucose (3H-Me-glc). We have found a drastic reduction in glucose uptake in different organs from male guinea pigs in vivo as well as in vitro. Female guinea pigs were less responsive to this effect of TCDD compared to males. Highly TCDD-responsive mice strains responded in the same way as the male guinea pigs, while less TCDD-responsive mice strains did not. A reduction in glucose uptake was found in explant adipose tissue cultures (in vitro) of male mice (highly TCDD-responsive) after a 4 hour incubation with 10(-8) M TCDD. In less responsive mice strains, stimulation was observed using the same model (in vitro). In the case of male rats, as well as male guinea pigs, glucose uptake was highly reduced by 10(-8) M TCDD using an in vitro system of explant adipose tissue. The Ah-receptor blocker, 4,7-phenanthroline, abolished the effect of TCDD on inhibition of glucose uptake in adipose tissue of male guinea pigs both in vivo and in vitro. Transcription and translation inhibitors (actinomycin D and cycloheximide, respectively) were tested separately or in combination with TCDD using the guinea pig adipose tissue culture model. It was found that actinomycin D could block the effect of TCDD on glucose uptake throughout the experiment time (360 min) while cycloheximide blocked TCDD action for about 60 minutes. Protein kinase inhibitors (e.g., genistein, neomycin) did not change the effect of TCDD on glucose uptake in male guinea pig adipose tissue. Based on these observations, we conclude that TCDD inhibits Me-glc uptake in various organs in guinea pigs, mice, and rats, and this response is mediated by the Ah-receptor.
通过使用一种不可代谢的葡萄糖类似物3-0-甲基-D-[1-³H]葡萄糖（³H-Me-glc），研究了2,3,7,8-四氯二苯并-p-二噁英（TCDD）对不同物种、性别和品系动物葡萄糖摄取的毒性作用。我们发现，无论是在体内还是体外，雄性豚鼠不同器官的葡萄糖摄取都大幅减少。与雄性相比，雌性豚鼠对TCDD的这种作用反应较小。对TCDD高度敏感的小鼠品系的反应与雄性豚鼠相同，而对TCDD反应较小的小鼠品系则没有这种反应。在与10⁻⁸ M TCDD孵育4小时后，雄性小鼠（对TCDD高度敏感）的外植脂肪组织培养物（体外）中发现葡萄糖摄取减少。在反应较小的小鼠品系中，使用相同模型（体外）观察到刺激作用。对于雄性大鼠以及雄性豚鼠，使用外植脂肪组织的体外系统时，10⁻⁸ M TCDD可使葡萄糖摄取大幅减少。芳烃受体阻滞剂4,7-菲咯啉在体内和体外均消除了TCDD对雄性豚鼠脂肪组织葡萄糖摄取抑制的作用。分别或与TCDD联合使用转录和翻译抑制剂（放线菌素D和环己酰亚胺）进行豚鼠脂肪组织培养模型试验。结果发现，放线菌素D在整个实验时间（360分钟）内均可阻断TCDD对葡萄糖摄取的作用，而环己酰亚胺在约60分钟内阻断TCDD的作用。蛋白激酶抑制剂（如染料木黄酮、新霉素）并未改变TCDD对雄性豚鼠脂肪组织葡萄糖摄取的作用。基于这些观察结果，我们得出结论，TCDD抑制豚鼠、小鼠和大鼠各种器官中的Me-glc摄取，且这种反应由芳烃受体介导。
