Release of glucose from the liver of fetal and postnatal sheep by portal vein infusion of catecholamines or glucagon.
1. The blood flow to the liver in fetuses near term, newborn and adult sheep was measured by the Fick principle, using radionuclide-labelled plastic microspheres, before and during infusion of adrenaline, noradrenaline or glucagon. 2. Glucose output and lactate consumption by the liver in sheep of each age group were calculated by application of the Fick principle using the concentration gradients of these metabolites measured in blood samples obtained, simultaneously with blood flow measurements, from catheters chronically implanted in the inflow and outflow vessels of the liver. 3. Catecholamines were infused into the portal vein of fetuses near term at a rate comparable with that at which they are known to be secreted in the sheep fetus during moderate to severe hypoxia. The cardiovascular and metabolic responses to these infusions were found to be comparable with those that occur in the fetus during hypoxia. 4. Catecholamines increased glucose output from the liver in all except the immediate post-partum animals. Catecholamines were less effective than glucagon in promoting glucose release. The mean increments in glucose output during adrenaline infusion were 0.055 +/- 0.015 mmol min-1 (100 g liver)-1 in the fetus, 0.122 +/- 0.024 mmol min-1 (100 g)-1 in the 2-week-old lambs, 0.078 +/- 0.019 mmol min-1 (100 g)-1 in young lambs and 0.049 +/- 0.012 mmol min-1 (100 g)-1 in the adult sheep. During glucagon infusion the mean glucose output increments were 0.146 +/- 0.023 mmol min-1 (100 g)-1 in the fetus, 0.274 +/- 0.085 mmol min-1 (100 g)-1 in the 2-week-old and young lambs and 0.180 +/- 0.054 mmol min-1 (100 g)-1 in the adult. Adrenaline was more potent than noradrenaline, suggesting that the major glycogenolytic response might be beta-receptor mediated. 5. In the immediate newborn period the output of glucose from the liver was high (0.20 +/- 0.05 mmol min-1 (100 g liver)-1 and was not statistically significantly increased by infusion either of glucagon or of catecholamines which resulted in similar increments of glucose output of about 0.128 +/- 0.133 mmol min-1 (100 g)-1. It is probable that the high output of glucose reflected the high endogenous circulating levels of catecholamines and glucagon in these animals at birth and that further infusions failed to add significantly to the already near-maximal glucose release.(ABSTRACT TRUNCATED AT 400 WORDS)
Apatu
R S
RS
Physiological Laboratory, Cambridge.
Barnes
R J
RJ
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D005333:Fetus / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D007773:Lactates / Q000097:blood; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D008112:Liver Glycogen / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D012756:Sheep
D007773:Lactates; D008112:Liver Glycogen; D005934:Glucagon; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine