Regulation of Glucose and Ammonia Production in the Isolated, Perfused Rat Kidney

Abstract

Renal gluconeogenesis in vitro is enhanced by increased [H+]. In Vivo, both acute and chronic metabolic acidosis are associated with increased NH₄ + excretion. Previous studies from our laboratory, using renal cortex slices, indicated that increased rates of ammonogenesis from glutamine are not dependent on corresponding changes in glucose production. The following studies have utilized perfusion of the isolated rat kidney to further investigate these interrelationships.

A modified, oxygen-saturated Krebs-Henseleit buffer, with added glutamine, was utilized as perfusate in an open system. The adequacy of this system was shown by the capacity to estalish a [H+] gradient, and constancy of urine flow, glomerular filtration (C+) and rates of gluconeogenesis for a period of two hours.

Glucose production and urinary ammonia excretion were markedly increased when the pH of perfusate was 7.1 as compared to 7.7. However, total ammonia production (effluent+urinary) was decreased at the acid pH. Addition of α-ketoglutarate or pyruvate to the perfusate led to expected increases in gluconeogenesis while total ammonia production decreased. Addition of glucose to the perfusate had no effect on total ammonia production from glutamine.

These studies indicate the following: (1) urinary ammonia excretion is not directly correlated with total ammonia production; (2) enhanced ammonia production is not an obligate consequence of increased glucose formation; (3) rates of ammonogenesis are regulated by changes in concentration of Krebs cycle intermediates.

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