Ethanol-induced hypoglycemia. I. The acute effects of ethanol on hepatic glucose output and peripheral glucose utilization in fasted dogs

Sixteen experiments were performed on dogs with chronic end-to-side portacaval shunts fasted 2 to 3 days to determine the acute effects of ethanol on hepatic glucose output and peripheral glucose utilization. Dogs with chronic end-to-side portacaval shunts were used since this preparation not only permits measurement of hepatic rather than splanchnic glucose balance but also allows calculation of peripheral glucose utilization. In 8 additional studies the effects of ethanol on splanchnic glucose output was determined in nonshunted healthy mongrel dogs fasted a similar period of time. Ethanol administered at mean rates varying from 0.029 to 0.183 mM/Kg./min. produced both a prompt (65 per cent) fall in mean hepatic glucose output and 25 per cent inhibition of peripheral glucose utilization. Hypoglycemia eventuated only when the magnitude of decrease in hepatic glucose output exceeded the magnitude of inhibition of peripheral glucose utilization. Splanchnic glucose balance during ethanol infusion also decreased significantly in dogs fasted for 2 to 3 days. These data show that ethanol-induced hypoglycemia is entirely the consequence of a decrease in the hepatic release of glucose. Its occurrence in glycogen-depleted starved dogs supports the hypothesis that ethanol inhibits hepatic gluconeogenesis, decreases hepatic release of glucose and thereby produces hypoglycemia. Since ethanol not only reduces hepatic glucose output but also inhibits peripheral glucose utilization, the failure to produce arterial hypoglycemia cannot be construed as evidence that ethanol does not consistently alter carbohydrate metabolism in fasted animals.