Acid-Base Alterations and Renal Gluconeogenesis: Effect of pH, Bicarbonate Concentration, and PCO2*

Abstract

In previous studies it was found that renal cortical slices from rats with induced metabolic acidosis have an increased capacity to produce glucose, whereas cortical slices from rats with metabolic alkalosis manifest decreased gluconeogenesis. To evaluate the relative influence of extracellular fluid pH, [HCO₃^-], and carbon dioxide tension on renal gluconeogenesis, we observed glucose production by cortex from rats with induced respiratory acidosis, and by cortex taken from normal animals and incubated in acid and alkaline media. We found glucose production to be increased in cortex from rats with respiratory acidosis, as is the case in metabolic acidosis. Glucose production by slices from normal rats was increased in media made acidic by reducing [HCO₃^-], and decreased in media made alkaline by raising [HCO₃^-]. These effects were evident whether the gluconeogenic substrate employed was glutamine, glutamate, α-ketoglutarate, or oxalacetate. Glucose production was also increased in media made acidic by raising CO₂ tension and decreased in media made alkaline by reducing CO₂ tension. These data indicate that both in vivo and in vitro, pH, rather than CO₂ tension or [HCO₃^-], is the most important acid-base variable affecting renal gluconeogenesis. The findings suggest that a decrease in extracellular fluid pH enhances renal gluconeogenesis through direct stimulation of one of the rate-limiting reactions involved in the conversion of oxalacetate to glucose. We hypothesize that the resultant increase in the rate of removal of glutamate, a precursor of oxalacetate, may constitute an important step in the mechanism by which acidosis increases renal ammonia production.