Influence of Glucagon on the Metabolism of Xylitol and Dihydroxyacetone in the Isolated Perfused Rat Liver

Glucagon stimulates glucose synthesis from xylitol and dihydroxyacetone in the isolated perfused rat liver. In addition to increasing the initial rate of glucose production from these substrates, the hormone also increases the efficiency of gluconeogenesis causing at least 90% of the substrate consumed by the liver to be converted to glucose. These effects of glucagon on gluconeogenesis are observed even when quinolinate is added to block entry of compounds through phosphoenolpyruvate carboxykinase. The formation of lactate from xylitol and oxidation of xylitol to CO2 are inhibited approximately 80% and 70%, respectively, by glucagon. Measurement of the steady-state concentrations of the gluconeogenic intermediates accompanying the stimulation of gluconeogenesis from xylitol and dihydroxyacetone show that the hormone markedly decreases the concentration of fructose 1,6-diphosphate. The mechanism by which glucagon causes the drastic fall in fructose-1,6-P2 cannot be explained in terms of the known allosteric regulation of fructose 1,6-diphosphatase and phosphofructokinase. The observations reported in this communication suggest that the effect of glucagon on gluconeogenesis and glycolysis is the result of a complex interaction rather than regulation of one particular enzyme of the gluconeogenic-glycolytic pathway.