Insulin is an important source of regulatory signals during fetal growth and development but alcohol exposure alters the metabolic and mitogenic responses of the fetus to insulin. The growth inhibition associated with fetal alcohol exposure is correlated with a lowered tissue glucose content and with decreases in basal glucose transport by the placenta and the fetus. However, alcohol-exposed embryos have a marked increase in glucose uptake in the presence of exogenous insulin when compared with vehicle-treated embryos. Insulin binding by the plasma membrane is increased in the alcohol-treated embryos but the binding of insulin-like growth factors is unchanged. The increase in insulin binding and in insulin-dependent glucose uptake notwithstanding, exposure to exogenous insulin further inhibits growth in alcohol-treated embryos but not in vehicle-treated embryos. Furthermore, fetal alcohol exposure leads to an abnormal insulin response in the adult offspring. these effects of alcohol cannot be completely overcome by glucose or caloric supplementation, suggesting that factors in addition to glucose uptake and metabolism are involved. Using nonplacental (chick) and placental (rat) embryos, cultured embryonic cells and adult animal exposed to alcohol in utero, the goals of the proposed research are to determine the molecular mechanism(s) by which alcohol alters the fetal and adult responses to insulin and to examine the physiological consequences of these molecular changes. The proposed studies will provide a basic understanding of the biochemical and physiological changes in the insulin response and in glucose homeostasis that result from fetal alcohol exposure. Because of their connection to human health, the studies are a logical prelude to the treatment or prevention of the effects of alcohol exposure during fetal development.
