LACTATE AND PYRUVATE STIMULATE THE CONVERSION OF GLUCOSE TO GLYCOGEN IN HEPATOCYTES BY A MECHANISM THAT DOES NOT INVOLVE GLUCONEOGENIC FLUX

Glycogen synthesis in hepatocytes was determined at various concentrat ions of CO2 and medium HCO3- to modulate cell pH. Glycogen synthesis f rom glucose was highest in acidic conditions (5% CO2/12.5 mM HCO3-) an d lowest in alkaline conditions (2.5% CO2/25 mM HCO3-). Physiological concentrations of lactate/pyruvate (2 mM/0.2 mM) stimulated the conver sion of glucose to glycogenin all media examined and mercaptopicolinat e, an inhibitor of gluconeogenesis, caused a similar stimulation as la ctate/pyruvate. In alkaline media, the stimulation by mercaptopicolina te and by lactate/pyruvate was additive, indicating that the latter is not due to gluconeogenic flux, In acidic media, the stimulation by bo th lactate/pyruvate and mercaptopicolinate was inhibited by amiloride, an inhibitor of Na+/H+ exchange. Since Na+/H+ exchange is activated w hen cell pH falls below a certain threshold, it is postulated that lac tate and pyruvate stimulate the conversion of glucose to glycogen thro ugh cellular acidification.