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 tetrachloro-dibenzo-p-dioxin (TCDD) as measured by quantificat ion of intracellular radioactivity in the NIH 3T3 L1 preadipocyte cell line after a 30-minute incubation with the nonmetabolizable radioacti ve analogue of glucose, 3-O-methyl-D-[1-H-3] glucose. Treatment of dif ferentiated NIH 3T3 L1 cells with TCDD produced a time- and dose-depen dent decrease in the cellular uptake of glucose. Treatment of cells fo r 3 hr with 10(-8) M TCDD significantly reduced glucose uptake to abou t 10% of control values (p less than or equal to 0.05). Furthermore, c ytochalasin B, a specific inhibitor of facilitative glucose transporte r proteins totally abolished the portion of glucose transport activity that is sensitive to TCDD. The role of the Ah receptor in TCDD-mediat ed reduction in glucose uptake was investigated. Pretreatment of 3T3 L 1 cells with the Ah receptor blocker 4,7-phenanthroline antagonized th e effects of TCDD on glucose uptake. Structure-activity relationship s tudies with TCDD and two polychlorinated biphenyl (PCB) congeners reve aled a rank order for their potency in the inhibition of glucose trans port as follows: TCDD << 3,3',4,4' tetrachlorobiphenyl <2,2',5,5' tetr achlorobiphenyl (TCB). Such a rank order correlates both with previous ly 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 t he Ah receptor. The thyroid hormone T-4, blocked the action of TCDD to further reduce glucose uptake. Experimental evidence is consistent wi th a proposed mechanism for TCDD to reduce the titer of functional glu cose transporter proteins through its interaction with the Ah receptor .