An Effect of Extracellular Redox State on the Glucagon-Stimulated Glucose Release by Rat Hepatocytes and Perfused Liver[*]

Abstract

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 µM-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 µM-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.

Key words

Redox-State - Glucagon Regulation - Glycogenolysis

1 This work was supported in part by a grant from the National Health and Medical Research Council of Australia.

1 This work was supported in part by a grant from the National Health and Medical Research Council of Australia.