An effect of extracellular redox state on the glucagon-stimulated glucose release by rat hepatocytes and perfused liver.

The effect of changes in the extracellular redox-state on glucagon-stimulated glucose release by intact isolated rat hepatocytes and the perfused liver was examined. For hepatocytes from the fed rat an increase in pyruvate, ammonium ion or oxygen concentration or a decrease in the lactate/pyruvate or sorbitol/fructose ratios decreased the ability of 1 microM-glucagon to stimulate glucose release without significantly altering the control rate. These changes coincided with a decrease in the lactate/pyruvate ratio of the cell suspension. A decrease in the lactate/pyruvate ratio also decreased the ability of 1 microM-glucagon to stimulate glycogen breakdown measured by loss of contained radioactivity. For the isolated perfused rat liver (fed rat) maximal effects of glucagon as a stimulant of glucose release occurred when lactate instead of pyruvate was present in the perfusion medium. It is concluded that the efficacy of glucagon as a stimulant of glucose release by isolated hepatocytes and the perfused liver depends upon the cytoplasmic redox-state represented by the intracellular lactate/pyruvate ratio.