Ethanol causes an acute and profound
insulin resistance in humans and in the rat. Recent studies indicate that defects in skeletal muscle
glucose uptake and utilization make a major contribution to this
insulin resistance. In this study, we used the euglycaemic hyperinsulinaemic clamp to examine the role that hepatic
ethanol oxidation via
alcohol dehydrogenase (ADH) plays in the acute
insulin resistance caused by
ethanol in the rat. Treatment with the ADH inhibitor
4-methylpyrazole (4-MP) failed to abolish the
insulin resistance as expressed as a decrease in the rate of
glucose infusion required to maintain euglycaemia (GIR). A decrease in GIR was also observed in response to
tert-butanol, an alcohol that is not a substrate for hepatic ADH. These results indicate that oxidation via ADH is not a prerequisite for the inhibition by
ethanol of whole-body
glucose utilization. In a separate study, we examined the relationship between blood
ethanol concentration and GIR in order to determine the potency of
ethanol in causing
insulin resistance. These experiments showed that even at low blood concentrations (<2 mM),
ethanol caused a profound decrease in GIR, similar in magnitude to that observed at higher blood concentrations (approximately 40 mM)