2,3,7,8-Tetrachlorodibenzo-p-dioxin causes reduction of glucose transporting activities in the plasma membranes of adipose tissue and pancreas from the guinea pig.
Toxicity from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure results in severe metabolic imbalances leading to a loss of fat stores in many animal species, a phenomenon known as the wasting syndrome. In this paper, we report that TCDD treatment at very low doses (0.03-1 micrograms/kg, single intraperitoneal injection) causes a profound reduction of glucose uptake by guinea pig adipose tissue, pancreas and brain. This effect of TCDD is dose-dependent, with a dose as small as 0.03 micrograms/kg resulting in a significant decrease. In adipose tissue, the decrease begins within 6 h of treatment and persists at least 28 days. The Vmax of glucose transport was decreased by TCDD treatment, whereas the Km was unchanged. Liver behaves oppositely to adipose tissue. At early stages of treatment (6-12 h) glucose uptake was depressed, while at later stages (24-96 h) it was increased. In situ (explant tissue culture) treatment with TCDD yields similar trends as in vivo studies for glucose uptake in all three tissues. In adipose tissue culture TCDD starts reducing glucose uptake after 30 minutes. The inhibitory potencies of three dioxin congeners on adipose glucose transporting activities follows the same order of their toxicities in vivo. TCDD's effect on glucose transport is sensitive to cytochalasin B, a specific inhibitor of glucose transporter proteins. Based on these observations and the importance of glucose transporters to cellular energy maintenance, we conclude that at least in guinea pigs the reduction of glucose transporters in various tissues is one of the major causes for TCDD-induced wasting syndrome, which is so prominent in this species.
Enan
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E
Department of Environmental Toxicology, University of California, Davis 95616.
Liu
P C
PC
Matsumura
F
F
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003571:Cytochalasin B / Q000494:pharmacology; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*
D001786:Blood Glucose; D009004:Monosaccharide Transport Proteins; D000072317:Polychlorinated Dibenzodioxins; D003571:Cytochalasin B