Separate effects of fatty acid oxidation and glucagon on gluconeogenesis in isolated hepatocytes from newborn pigs.

In hepatocytes isolated from 48-hour-old suckling pigs, the inhibition of endogenous fatty acid oxidation leads to a 30% inhibition of glucose production from lactate. Addition of oleate plus carnitine to hepatocytes from 48-hour-old fasting pigs increases by 30% the rate of gluconeogenesis from lactate. In hepatocytes isolated from fasting newborn pigs, addition of glucagon (0.5 ng/ml) produces a 30% increase in the rate of glucose production from lactate and a 70% increase of glucose synthesis from dihydroxyacetone. The high rate of lactate plus pyruvate production in fasting piglets is markedly suppressed by glucagon and return to the value measured in suckling newborns. Combined addition of oleate and glucagon to hepatocytes from fasting piglets increases by 2-fold the rate of glucose production from lactate but does not restore totally the rate of glucose synthesis found in suckling piglets. It is concluded that fatty acid oxidation and hormonal environment contribute significantly to the development of an active gluconeogenesis in the newborn pig but do not represent the sole factors involved in the regulation of hepatic gluconeogenesis.