Regulation of glucose transport in the NIH 3T3 L1 preadipocyte cell line by TCDD

Environ Health Perspect. 1994 May;102(5):454-8. doi: 10.1289/ehp.94102454.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Adipose Tissue / cytology
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Biological Transport, Active / drug effects
  • Drug Interactions
  • Environmental Pollutants / toxicity*
  • Glucose / metabolism*
  • Hormones / pharmacology
  • Kinetics
  • Mice
  • Monosaccharide Transport Proteins / metabolism
  • Phenanthrolines / pharmacology
  • Polychlorinated Dibenzodioxins / toxicity*
  • Receptors, Aryl Hydrocarbon / antagonists & inhibitors
  • Receptors, Aryl Hydrocarbon / drug effects
  • Receptors, Aryl Hydrocarbon / metabolism

Substances

  • Environmental Pollutants
  • Hormones
  • Monosaccharide Transport Proteins
  • Phenanthrolines
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • 4,7-phenanthroline
  • Glucose