Studies on the Regulation of Gluconeogenesis in Isolated Rat Liver Cells by Epinephrine and Glucagon

Abstract The addition of glucagon or epinephrine to isolated rat liver parenchymal cells stimulated gluconeogenesis from alanine, lactate, glycerol, xylitol, oxalacetate, pyruvate, and fructose. The stimulation of gluconeogenesis due to maximal concentrations of epinephrine was additive to that of either glucagon or N6, O2'-dibutyryl adenosine 3' : 5'-monophosphate (dibutyryl cyclic AMP). Similarly low concentrations of valinomycin and lysine stimulated gluconeogenesis but the same increases in glucose production due to epinephrine, glucagon, or dibutyryl cyclic AMP were seen in the presence as in the absence of lysine or valinomycin. However, the stimulation of glucose production due to glucagon was not additive to that of dibutyryl cyclic AMP. Gluconeogenesis was reduced by the absence of K+ or Ca2+ from the buffer. The addition of 0.65 mm Ca2+ or 2.4 mm K+ restored basal gluconeogenesis and the response to epinephrine or dibutyryl cyclic AMP. The effect of epinephrine was potentiated by increasing the Ca2+ concentration from 0.65 to 2.6 mm. The addition of ouabain to liver cells had effects similar to those seen when K+ was omitted from the buffer. These results indicate that the stimulation of gluconeogenesis by glucagon or epinephrine is not restricted to substrates which enter the pathways of glucose formation prior to phosphoenolpyruvate, and support the hypothesis that epinephrine mediated gluconeogenesis occurs by a cyclic adenosine 3' : 5'-monophosphate-independent mode of action distinct from that for glucagon.