TY - JOUR
T1 - Epinephrine-induced changes in hepatic glucose production after ethanol
AU - Lang, C. H.
AU - Molina, P. E.
AU - Skrepnick, N.
AU - Bagby, G. J.
AU - Spitzer, J. J.
PY - 1994
Y1 - 1994
N2 - 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 μg · 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. These results indicate that EtOH alters hepatic glucose production in response to epinephrine. These data imply that the ability of EtOH to alter glucose metabolism after endotoxin is independent of EtOH metabolism and is due to a decreased responsiveness of the liver to adrenergic stimulation.
AB - 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 μg · 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. These results indicate that EtOH alters hepatic glucose production in response to epinephrine. These data imply that the ability of EtOH to alter glucose metabolism after endotoxin is independent of EtOH metabolism and is due to a decreased responsiveness of the liver to adrenergic stimulation.
UR - http://www.scopus.com/inward/record.url?scp=0027974374&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027974374&partnerID=8YFLogxK
U2 - 10.1152/ajpendo.1994.266.6.e863
DO - 10.1152/ajpendo.1994.266.6.e863
M3 - Article
C2 - 8023915
AN - SCOPUS:0027974374
SN - 0193-1849
VL - 266
SP - E863-E869
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 6 29-6
ER -