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Decreased glucose transporter 1 gene expression and glucose uptake in fetal brain exposed to ethanol
S P Singh1, G L Pullen, K S Srivenugopal
1Endocrine-Metabolic Division, Veterans Affairs Medical Center, North Chicago, Illinois 60064.
Using pregnant rats fed equicaloric liquid diets (AF, and libitum-fed controls; PF, pair-fed controls; EF, ethanol-fed), we have previously shown that maternal alcoholism produces a specific and significant decrease of glucose in the fetal brain, which is accompanied by growth retardation. To further define the mechanisms of ethanol-induced perturbations in fetal fuel supply, we have examined (i) the uptake of 2-deoxyglucose (2-DG) by dissociated brain cells from fetal rats that were exposed to ethanol in utero and (ii) the steady-state levels of the glucose transporter-1 (GT-1) mRNA. A 9% decrease in brain weight (P less than 0.001) and a 54.8% reduction in 2-DG uptake into brain cells (P less than 0.02) were found in offspring of EF mothers compared to the AF group. Brain weight correlated with the rate of 2-DG uptake (P less than 0.05). Northern blot analysis showed a 50% reduction of GT-1 mRNA in EF brain relative to that in the AF and PF groups. We conclude that glucose transport into the brain is an important parameter altered by maternal ethanol ingestion.
Using pregnant rats fed equicaloric liquid diets (AF, and libitum-fed controls; PF, pair-fed controls; EF, ethanol-fed), we have previously shown that maternal alcoholism produces a specific and significant decrease of glucose in the fetal brain, which is accompanied by growth retardation. To further define the mechanisms of ethanol-induced perturbations in fetal fuel supply, we have examined (i) the uptake of 2-deoxyglucose (2-DG) by dissociated brain cells from fetal rats that were exposed to ethanol in utero and (ii) the steady-state levels of the glucose transporter-1 (GT-1) mRNA. A 9% decrease in brain weight (P less than 0.001) and a 54.8% reduction in 2-DG uptake into brain cells (P less than 0.02) were found in offspring of EF mothers compared to the AF group. Brain weight correlated with the rate of 2-DG uptake (P less than 0.05). Northern blot analysis showed a 50% reduction of GT-1 mRNA in EF brain relative to that in the AF and PF groups. We conclude that glucose transport into the brain is an important parameter altered by maternal ethanol ingestion.