2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced changes in glucose transporting activity in guinea pigs, mice, and rats in vivo and in vitro. 1994

E Enan, and F Matsumura
Department of Environmental Toxicology, University of California, Davis 95616.

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.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D005260 Female Females
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000072317 Polychlorinated Dibenzodioxins Dibenzodioxin derivatives that contain multiple chloride atoms bound to the benzene ring structures. TCDD,Tetrachlorodibenzodioxin,2,3,7,8-Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo-p-dioxins,Dibenzo(b,e)(1,4)dioxin, 2,3,7,8-tetrachloro-,PCDD,Polychlorinated Dibenzo-p-dioxins,Polychlorinated Dibenzodioxin,Polychlorodibenzo-4-dioxin,Polychlorodibenzo-p-dioxin,Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo p dioxins,Dibenzo-p-dioxins, Chlorinated,Dibenzo-p-dioxins, Polychlorinated,Dibenzodioxin, Polychlorinated,Dibenzodioxins, Polychlorinated,Polychlorinated Dibenzo p dioxins,Polychlorodibenzo 4 dioxin,Polychlorodibenzo p dioxin,Tetrachlorodibenzo p dioxin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic

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