Ethanol oxidation is not required to attenuate endotoxin-enhanced glucose metabolism.
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 micrograms/100 g body wt) increased glucose rate of appearance (Ra) 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 Ra or MCR. Furthermore, the injection of the nonmetabolized alcohol tert-butanol abolished the endotoxin-induced increase in glucose Ra and MCR without preventing the endotoxin-induced hyperglycemia and hyperlactacidemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Molina
P E
PE
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Lang
C H
CH
Bagby
G J
GJ
Spitzer
J J
JJ
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D000440:Butanols / Q000378:metabolism / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D000431:Ethanol / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D006439:Hemodynamics; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D020002:tert-Butyl Alcohol
D000440:Butanols; D004731:Endotoxins; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D005947:Glucose; D020002:tert-Butyl Alcohol