Control of lactate utilization by extracellular pH in isolated rat liver cells

This study reports the influence of external pH on lactate balance in hepatocytes isolated from fed and 24-hour-starved rats. The effects of changes in extracellular pH on the utilization of lactate by liver cells has been studied in conditions simulating metabolic acidosis (pH 7.15, 10 mmol/L bicarbonate). The addition of lactate to a suspension of liver cells from fed rats shifted the lactate balance from net release to net utilization; the threshold of this shift was about 3 mmol/L in the presence of 10 mmol/L glucose. In these cells, acidic external pH (7.15) played a crucial role in stimulating the lactate utilization as shown by (1) a diminished release of lactate in the absence of lactate addition (-60%); (2) a marked decrease of the threshold of lactate utilization down to 1.2 mmol/L; and (3) a net stimulation of the lactate utilization for concentrations in the physiologic range (2 to 3 mmol/L). The effect of acidosis was mediated by an inhibition of glycolysis (-40%). Besides that, at pH 7.45, the addition of 100 mumol/L AICA-riboside 5-amino-4-imidazolecarboxamide riboside, (an inhibitor of hepatic glycolysis) mimicked the effect of acidosis. Moreover, differences in lactate fluxes between the two pH conditions were decreased in the absence of glucose. In liver cells from starved rats, regardless of the concentration of added lactate, the lactate balance was always directed toward net utilization. Accordingly, a change in external pH from 7.45 to 7.15 had a lesser effect on lactate metabolism than in liver cells from fed rats.(ABSTRACT TRUNCATED AT 250 WORDS)