Insulin signaling in chick embryos exposed to alcohol.
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)
Pennington
S N
SN
Department of Biochemistry, East Carolina University, School of Medicine, Greenville, North Carolina 27858, USA.
Shibley
I A
IA
Koochek
K
K
Gavigan
M D
MD
Monaghan
J M
JM
Sandstrom
L P
LP
Morgan
J L
JL
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002642:Chick Embryo; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D007328:Insulin / Q000502:physiology*; D009955:Ornithine Decarboxylase / Q000502:physiology; D019000:Phosphotyrosine / Q000378:metabolism; D011972:Receptor, Insulin / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013002:Somatomedins / Q000502:physiology
D001786:Blood Glucose; D007328:Insulin; D013002:Somatomedins; D019000:Phosphotyrosine; D011972:Receptor, Insulin; D009955:Ornithine Decarboxylase