Regulation of glucose transport in the NIH 3T3 L1 preadipocyte cell line by TCDD.
This study examined the changes in cellular glucose uptake induced by 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) as measured by quantification of intracellular radioactivity in the NIH 3T3 L1 preadipocyte cell line after a 30-minute incubation with the non-metabolizable radioactive analogue of glucose, 3-O-methyl-D-[1-3H] glucose. Treatment of differentiated NIH 3T3 L1 cells with TCDD produced a time- and dose-dependent decrease in the cellular uptake of glucose. Treatment of cells for 3 hr with 10(-8) M TCDD significantly reduced glucose uptake to about 10% of control values (p </= 0.05). Furthermore, cytochalasin B, a specific inhibitor of facilitative glucose transporter proteins totally abolished the portion of glucose transport activity that is sensitive to TCDD. The role of the Ah receptor in TCDD-mediated reduction in glucose uptake was investigated. Pretreatment of 3T3 L1 cells with the Ah receptor blocker 4,7-phenanthroline antagonized the effect of TCDD on glucose uptake. Structure-activity relationship studies with TCDD and two polychlorinated biphenyl (PCB) congeners revealed a rank order for their potency in the inhibition of glucose transport as follows: TCDD <<3,3',4,4' tetrachlorobiphenyl <2,2',5,5' tetrachlorobiphenyl (TCB). Such a rank order correlates both with previously determined biological activity of TCDD and the more active 3,3',4,4'- and less active 2,2',5,5'-TCB and with affinity for binding to the Ah receptor. The thyroid hormone T4, like TCDD, reduced glucose uptake and blocked the action of TCDD to further reduce glucose uptake. Experimental evidence is consistent with a proposed mechanism for TCDD to reduce the titer of functional glucose transporter proteins through its interaction with the Ah receptor.
Olsen
H
H
Department of Environmental Toxicology, University of California-Davis 95620, USA.
Enan
E
E
Matsumura
F
F
D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004347:Drug Interactions; D004785:Environmental Pollutants / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism*; D006728:Hormones / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010618:Phenanthrolines / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism
D004785:Environmental Pollutants; D006728:Hormones; D009004:Monosaccharide Transport Proteins; D010618:Phenanthrolines; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; C053487:4,7-phenanthroline; D005947:Glucose