Actions of glucagon on flux rates in perfused rat liver. 2. Relationship between inhibition of glycolysis and stimulation of respiration by glucagon.

The relationship between inhibition of glycolysis and stimulation of oxygen consumption by glucagon was studied in perfused rat livers. The two effects exhibit similar kinetics and dose-response curves; they are slower and less sensitive to the glucagon concentration than the stimulatory effect on glycogenolysis. A stoichiometry of 1 mol extra oxygen consumed/1.8 mol of diminished lactate plus pyruvate production was found. Under conditions where glucagon did not cause a marked inhibition of glycolysis (i.e. low glycolytic flux rates in the fasted state or in the presence of ethanol), oxygen consumption was also not markedly increased. These findings provide evidence that the major portion of glucagon-induced stimulation of hepatic respiration in the fed state is due to an enhanced demand for mitochondrial oxidative phosphorylation to compensate for the diminished extramitochondrial ATP production following inhibition of glycolysis by glucagon.