ACUTE ETHANOL-MEDIATED INSULIN-RESISTANCE IN THE RAT - THE ROLE OF ETHANOL OXIDATION

Ethanol causes an acute and profound insulin resistance in humans and in the rat. Recent studies indicate that defects in skeletal muscle gl ucose uptake and utilization maize a major contribution to this insuli n 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 et hanol in the rat. Treatment with the ADH inhibitor 4-methylpyrazole (4 -MP) failed to abolish the insulin resistance as expressed as a decrea se in the rate of glucose infusion required to maintain euglycaemia (G IR). A decrease in GIR was also observed in response to tert-butanol, an alcohol that is not a substrate for hepatic ADH. These results indi cate that oxidation via ADH is not a prerequisite for the inhibition b y ethanol of whole-body glucose utilization. In a separate study, we e xamined the relationship between blood ethanol concentration and GIR i n order to determine the potency of ethanol in causing insulin resista nce. These experiments showed that even at low blood concentrations (< 2 mM), ethanol caused a profound decrease in GIR, similar in magnitud e to that observed at higher blood concentrations (approximately 40 mM )