The interrelationship of the concentration of hydrogen ions, bicarbonate ions, carbon dioxide and calcium ions in the regulation of renal gluconeogenesis in the rat

The interrelationship of acidosis and Ca²⁺ on the stimulation of gluconeogenesis by rat kidney cortex slices was studied. Ca²⁺ stimulated gluconeogenesis from glutamine, glutamate, 2 oxoglutarate, succinate, malate, pyruvate, lactate and fructose, but not from galactose. The [Ca²⁺] needed for optimum gluconeogenesis was about 2 mM, but at this concentration, acidosis, produced in vitro by a decrease of [HCO₃-] in the medium at constant pCO₂ or by an increase in pCO₂ at constant [HCO₃-], did not stimulate gluconeogenesis. In the absence of Ca²-, acidosis (low [HCO₃-]) stimulated gluconeogenesis from glutamine, glutamate, 2 oxoglutarate, succinate, malate, pyruvate and lactate but not from fructose or galactose. With succinate as substrate, the stimulatory effect of acidosis (low [HCO₃-]) disappeared at Ca²⁺ concentrations above 1.0 mM. The [HCO₃-] was the most important determinant of the acidosis effect since a decrease of pH caused by an increase in pCO₂ did not uniformly stimulate gluconeogenesis, whereas a decrease in [HCO₃-] without a change in pH consistently stimulated glucose formation in a way similar to the stimulation produced by acidosis (low [HCO₃ ^-]) in the absence of Ca²⁺. Acidosis in vitro inhibited the rate of decrease of activity of phosphoenolpyruvate carboxylase in slices, and Ca²⁺ caused an increase in the activity of fructose 1 phosphate aldolase. Respiratory acidosis in vitro caused an increase in the activity of phosphoenolpyruvate carboxylase in kidney cortex and an increase in gluconeogenesis from glutamine. Possible points of interaction between Ca²⁺, H⁺ and HCO₃- with the gluconeogenic sequence are discussed.