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Insulin signaling in chick embryos exposed to alcohol
S N Pennington1, I A Shibley, K Koochek
1Department of Biochemistry, East Carolina University, School of Medicine, Greenville, North Carolina 27858, USA.
Insights
Fetal alcohol exposure increases insulin receptor numbers and insulin-dependent glucose uptake in chick embryos. However, alcohol-disrupted development impairs normal cellular responses to insulin, indicating complex effects beyond glucose transport.
Area of Science:
- Developmental Biology
- Endocrinology
- Toxicology
Background:
- Insulin regulates fetal growth, but alcohol's effects on insulin action are unclear.
- Fetal alcohol exposure in rats leads to abnormal glucose metabolism later in life.
- Alcohol-induced fetal growth restriction involves impaired placental glucose transport.
Purpose of the Study:
- To investigate the impact of fetal alcohol exposure on insulin action in a controlled embryonic model.
- To determine if alcohol affects insulin binding, receptor number, or affinity.
- To assess glucose uptake and cellular responses to insulin in alcohol-exposed embryonic tissues.
Main Methods:
- Utilized an embryonic chick model to isolate alcohol's direct effects, bypassing maternal/placental factors.
- Measured insulin and insulin-like growth factor binding to embryonic tissues.
- Quantified insulin receptor number and affinity using competitive binding assays.
- Assessed basal and insulin-stimulated 2-deoxyglucose uptake.
- Measured ornithine decarboxylase activity as an indicator of cellular response.
Main Results:
- Fetal alcohol exposure significantly increased insulin binding and insulin receptor numbers in embryonic tissues.
- Alcohol exposure did not alter insulin-like growth factor binding or insulin receptor affinity.
- Basal glucose uptake was reduced by alcohol, but insulin stimulation increased uptake in exposed embryos.
- Exogenous insulin failed to normalize ornithine decarboxylase activity in alcohol-exposed cells.
Conclusions:
- Fetal alcohol exposure enhances insulin receptor expression and insulin-mediated glucose uptake in developing chick embryos.
- Despite increased insulin sensitivity, alcohol disrupts downstream cellular signaling pathways, preventing normal development.
- These findings highlight complex, multifaceted effects of prenatal alcohol exposure on endocrine regulation and embryonic development.
Abstract:
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 maternal/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 x 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.(ABSTRACT TRUNCATED AT 250 WORDS)