TCDD (2,3,7,8-tetrachlorodibenzo-P-dioxin) causes reduction in glucose uptake through glucose transporters on the plasma membrane of the guinea pig adipocyte.
A single dose of 2,3,7,8-TCDD (1 micrograms/kg, i.p. injection) resulted in a significant decrease in cellular 3-O-methyl-[3H]-glucose uptake by guinea pig adipose tissue and pancreas after 24 hours. An in situ tissue culture study in which pieces of adipose tissue were incubated with 10(-8)M TCDD showed a time-dependent decrease in glucose uptake. Reconstitution of adipocyte plasma membrane from tested or control animals into artificial liposomes also resulted in this difference in glucose uptake. Binding of [3H]-cytochalasin B, a specific inhibitor of glucose transporter proteins, was significantly lower in acetone-ether powder preparations of TCDD-treated adipose tissue than from controls, suggesting that the total titer of these proteins is decreased by TCDD. Finally, the relevance of these results to glucose or lipid metabolism was tested. Lipoprotein lipase (LPL) activity of guinea pig adipose tissue was decreased after 8 hours of in situ incubation with TCDD indicating that glucose uptake was depressed at an earlier time point. These findings may contribute to a better understanding of dioxin-induced "wasting syndrome".
Enan
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Dept. of Environmental Toxicology, University of California, Davis 95620.
Liu
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PC
Matsumura
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D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003571:Cytochalasin B / Q000494:pharmacology; D005947:Glucose / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000187:drug effects*; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000009:adverse effects*
D009004:Monosaccharide Transport Proteins; D000072317:Polychlorinated Dibenzodioxins; D003571:Cytochalasin B; D005947:Glucose