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.
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D005632:Fructose / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen; D010477:Perfusion; D011773:Pyruvates / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D013012:Sorbitol / Q000494:pharmacology
D007773:Lactates; D008112:Liver Glycogen; D011773:Pyruvates; D000643:Ammonium Chloride; D005632:Fructose; D013012:Sorbitol; D005934:Glucagon; D005947:Glucose; D010100:Oxygen