KETONE-BODIES ACTIVATE GLUCONEOGENESIS IN ISOLATED RABBIT RENAL CORTICAL TUBULES INCUBATED IN THE PRESENCE OF AMINO-ACIDS AND GLYCEROL

In isolated rabbit renal kidney-cortex tubules 2 mM glycerol, which is a poor gluconeogenic substrate, does not induce glucose formation in the presence of alanine, while it activates gluconeogenesis on substit ution of alanine by aspartate, glutamate or proline. The addition of e ither 5 mM 3-hydroxybutyrate or 5 mM acetoacetate to renal tubules inc ubated with alanine+glycerol causes a marked induction of glucose prod uction associated with inhibition of glutamine synthesis. In contrast, the rate of the latter process is not altered by ketones in the prese nce of glycerol and either aspartate, glutamine or proline despite the stimulation of glucose formation. Acceleration of gluconeogenesis by ketone bodies in the presence of amino acids and glycerol is probably due to (i) stimulation of pyruvate carboxylase activity, (ii) activati on of malate-aspartate shuttle as concluded from elevated intracellula r levels of malate, aspartate and glutamate, as well as (iii) diminish ed supply of ammonium for glutamine synthesis from alanine resulting f rom a decrease in glutamate dehydrogenase activity.