Although insulin is known to be an important generator of regulatory s
ignals during fetal growth and development, neither the immediate nor
long-term effects of alcohol (ethanol) on insulin action are well unde
rstood. in the rat, fetal exposure to alcohol has been shown to be cor
related with a subsequent abnormal response to a glucose load in the n
eonate and adult. Further, fetal hypoplasia secondary to maternal alco
hol consumption is correlated with decreased placental glucose transpo
rt and with a lowering of the glucose levels in fetal tissues. However
, the fetal effects of alcohol cannot be completely overcome by glucos
e/caloric supplementation, suggesting that factors other than glucose
transport are involved. Using an embryonic chick model that negates th
e factors of maternal/placental metabolism and transport, the current
study found that fetal alcohol exposure markedly increased insulin bin
ding in developing tissue, but had little effect on the binding of the
insulin-like growth factors. Competitive binding experiments revealed
a marked increase in insulin receptor numbers, but no change in bindi
ng affinity as a result of the alcohol exposure. Basal uptake of 2-deo
xyglucose by fetal tissue was lowered by alcohol exposure, but incubat
ion with exogenous porcine insulin (1 x 10(-7) M) resulted in a signif
icant increase in glucose uptake by the alcohol-exposed embryos. The i
ncreases in insulin binding and in insulin-dependent glucose uptake no
twithstanding, exogenous insulin could not induce normal levels of orn
ithine decarboxylase activity in embryonic cells previously exposed to
alcohol. Furthermore, insulin treatment seemed to inhibit growth in a
lcohol-exposed whole embryos. Molecular changes in the insulin signali
ng cascade occurring as the result of alcohol exposure included an inc
rease in specific phosphotyrosine content that was markedly decreased
following insulin stimulation. The decrease in phosphotyrosine content
did not seem to involve the insulin receptor substrate-1:phosphoinosi
tol-3 (PI-3) kinase complex, because alcohol-treated embryos had signi
ficantly elevated basal PI-3 kinase activity that was not altered by i
nsulin exposure. In summary, alcohol-induced growth suppression in the
chick embryo is associated with several changes in insulin signaling
and thus data suggest that this important mitogenic pathway is impaire
d as the result of fetal alcohol exposure.