Previous studies from our laboratory demonstrated that acute ethanol (EtOH) intoxication, through an unknown mechanism, blunts the endotoxin-enhanced carbohydrate metabolism. The purpose of the present study was to determine whether oxidation of the ethanol moiety is required for the inhibition of the endotoxin-induced changes in carbohydrate metabolism. In vivo glucose kinetics were assessed by the intravenous administration of D-[3-3H]glucose in catheterized conscious unrestrained rats. Escherichia coli endotoxin (200 μg/100 g body wt) increased glucose rate of appearance (R(a)) and metabolic clearance rate (MCR) by 75 and 50%, respectively. A primed-constant infusion of EtOH (275 mg/100 g + 25 mg·100 g-1·h-1) initiated 2 h before endotoxin challenge attenuated the endotoxin-enhanced glucose kinetics. EtOH intoxication did not prevent endotoxin-induced hyperglycemia but delayed the hyperlactacidemic response. The importance of EtOH metabolism in suppressing the glucose metabolic response to endotoxin was studied by administering 4-methyl-pyrazole (4-MP; 8 mg/100 g), an inhibitor of alcohol dehydrogenase activity. After administration of 4-MP and a bolus injection of EtOH (275 mg/100 g), the plasma EtOH concentration remained constant and matched the level of EtOH in rats receiving a primed-constant infusion of EtOH. Inhibition of EtOH metabolism with 4-MP did not abrogate the ability of EtOH to suppress endotoxin-induced increases in glucose R(a) or MCR. Furthermore, the injection of the nonmetabolized alcohol tert-butanol abolished the endotoxin-induced increase in glucose R(a) and MCR without preventing the endotoxin-induced hyperglycemia and hyperlactacidemia. These results indicate that the ability of EtOH to suppress changes in carbohydrate metabolism in response to endotoxin challenge is independent of EtOH metabolism and its metabolic end products.
|Original language||English (US)|
|Journal||American Journal of Physiology - Regulatory Integrative and Comparative Physiology|
|Issue number||6 29-6|
|State||Published - Jan 1 1991|
All Science Journal Classification (ASJC) codes
- Physiology (medical)