Oxygenation does not stimulate hepatic gluconeogenesis in fetal lambs

We have previously shown that the healthy fetal lamb liver does not release glucose and does not demonstrate gluconeogenesis. Shortly after birth, however, the liver releases glucose both by glycogenolysis and by gluconeogenesis. Previously it has been suggested that increased oxygen availability stimulates hepatic gluconeogenesis at birth. To test this hypothesis, we increased fetal arterial blood pO2 by ventilating the fetus with high oxygen gas mixtures in utero. We placed intravascular catheters in the right or left hepatic vein, umbilical vein, inferior vena cava, and descending aorta and inserted a large polyvinyl tube into the trachea of seven fetal lambs at 134 +/- 2.2 days gestation. Studies were done several days after surgery. 14C-lactate was infused intravenously and 14C-glucose concentrations were measured in hepatic venous and umbilical venous blood during a control period, during ventilation with 5% CO2, 3% O2, 92% N2, and then during ventilation with 5% CO2 and 95% O2. The difference between these two measurements represented hepatic gluconeogenesis. Arterial blood glucose concentrations and blood gases were also measured during each study period. Ventilation with 3% O2 did not significantly change arterial PO2 but ventilation with 95% oxygen increased mean arterial pO2 from a control of 16.7 to 156.3 torr. Mean arterial blood glucose concentration increased significantly from a control of 11.9 to 17.6 mg/dl during ventilation with 3% O2 and to 19.1 mg/dl during ventilation with 95% O2. However, the hepatic-umbilical venous 14C-glucose concentration difference was not significant when control values were compared with each ventilation period. We conclude that an acute increase in fetal oxygenation does not stimulate hepatic gluconeogenesis in near-term fetal lambs.