Although insulin is known to be an important generator of regulatory signals during fetal growth and development, neither the immediate nor long‐term effects of alcohol (ethanol) on insulin action are well understood. In the rat, fetal exposure to alcohol has been shown to be correlated with a subsequent abnormal response to a glucose load In the neonate and adult. Further, fetal hypoplasia secondary to maternal alcohol consumption is correlated with decreased placental glucose transport and with a lowering of the glucose levels in fetal tissues. However, the fetal effects of alcohol cannot be completely overcome by glucose/caloric supplementation, suggesting that factors other than glucose transport are involved. Using an embryonic chick model that negates the factors of matemal/placental metabolism and transport, the current study found that fetal alcohol exposure markedly increased insulin binding 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 binding affinity as a result of the alcohol exposure. Basal uptake of 2‐deoxyglucose by fetal tissue was lowered by alcohol exposure, but incubation with exogenous porcine insulin (1 ± 10 ‐7 m) resulted in a significant increase in glucose uptake by the alcohol‐exposed embryos. The increases in insulin binding and in insulin‐dependent glucose uptake notwithstanding, exogenous insulin could not induce normal levels of ornithine decarboxylase activity in embryonic cells previously exposed to alcohol. Furthermore, insulin treatment seemed to inhibit growth in alcohol‐exposed whole embryos. Molecular changes in the insulin signaling cascade occurring as the result of alcohol exposure included an increase 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:phosphoinositol‐3 (PI‐3) kinase complex, because alcohol‐treated embryos had significantly elevated basal PI‐3 kinase activity that was not altered by insulin 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 impaired as the result of fetal alcohol exposure.
|Original language||English (US)|
|Number of pages||7|
|Journal||Alcoholism: Clinical and Experimental Research|
|State||Published - Jun 1995|
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Psychiatry and Mental health