Epinephrine-induced changes in hepatic glucose production after ethanol.
Previous studies indicate that catecholamines play an important role in mediating the glucose metabolic response to endotoxin. Because acute ethanol (EtOH) intoxication impairs this response, the present study was initiated to ascertain whether EtOH attenuates the lipopolysaccharide response by decreasing the increment in plasma catecholamines after endotoxin or by decreasing the responsiveness of rats to epinephrine. All studies were performed on chronically catheterized fasted rats infused intravenously with either EtOH or an equal volume of saline. In the first series of experiments, intravenous administration of Escherichia coli endotoxin increased, to the same extent, the plasma concentrations of epinephrine and norepinephrine in both saline- and EtOH-infused rats. In the second study, rats were infused with [3-3H]glucose to assess whole body glucose metabolism and the ability of EtOH to alter the glucose metabolic response to epinephrine. The exogenous infusion of a maximally stimulating dose of epinephrine (1 microgram.min-1.kg-1) into saline-infused control animals for 3 h produced a marked hyperglycemia that resulted from a sustained increase in the rate of hepatic glucose production and a reduction in the metabolic clearance rate for glucose. EtOH infusion did not prevent the epinephrine-induced hyperglycemia but blunted the stimulatory effect of epinephrine on glucose production. The differences in glucose metabolism between saline- and EtOH-treated rats could not be explained by changes in plasma insulin or glucagon concentrations. Furthermore, the ability of EtOH to impair the epinephrine-induced increase in glucose production was still evident in rats treated with 4-methylpyrazole, an inhibitor of alcohol dehydrogenase.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
C H
CH
Lang
P E
PE
Molina
N
N
Skrepnick
G J
GJ
Bagby
J J
JJ
Spitzer
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood / Q000494:pharmacology*; D004926:Escherichia coli; D000431:Ethanol / Q000494:pharmacology*; D000077604:Fomepizole; D005947:Glucose / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004731:Endotoxins; D011720:Pyrazoles; D000431:Ethanol; D000077604:Fomepizole; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine