Oxygenation does not stimulate hepatic gluconeogenesis in fetal lambs

Area of Science:

• Perinatal Physiology
• Neonatal Metabolism
• Hepatic Function

Background:

• The fetal lamb liver does not produce glucose, but it does shortly after birth via glycogenolysis and gluconeogenesis.
• Increased oxygen availability at birth has been hypothesized to stimulate hepatic gluconeogenesis.

Purpose of the Study:

• To investigate whether acute increases in fetal oxygenation stimulate hepatic gluconeogenesis in near-term fetal lambs.
• To test the hypothesis that elevated oxygen levels trigger glucose production in the fetal liver.

Main Methods:

• Seven fetal lambs (134 +/- 2.2 days gestation) underwent surgery for intravascular catheter placement and tracheal intubation.
• 14C-lactate was infused, and 14C-glucose concentrations were measured in hepatic and umbilical venous blood.
• Fetal lambs were ventilated with varying oxygen (O2) and carbon dioxide (CO2) mixtures to alter blood oxygen levels (pO2).

Main Results:

• Ventilation with 95% O2 significantly increased mean arterial pO2 from 16.7 to 156.3 torr.
• Arterial blood glucose concentrations increased during both low (3% O2) and high (95% O2) ventilation periods.
• No significant difference was observed in the hepatic-umbilical venous 14C-glucose concentration difference between control and ventilation periods.

Conclusions:

• Acute increases in fetal oxygenation do not stimulate hepatic gluconeogenesis in near-term fetal lambs.
• The study challenges the hypothesis that increased oxygen availability is a primary trigger for hepatic gluconeogenesis at birth.