The inhibitory effect of octanoate, palmitate and oleate on glucose formation in rabbit kidney tubules.

The effect of octanoate, palmitate and oleate on glucose formation was studied with lactate, pyruvate or malate as substrate in kidney tubules isolated from fasted rabbits. All fatty acids studied inhibited the rate of glucose production by about 30-50% depending on the glucose precursor and fatty acid used, stimulated the oxygen uptake by about 50% and increased the mitochondrial NADH/NAD+ ratio, as manifested by a marked rise of 3-hydroxybutyrate/acetoacetate ratio. Octanoate was twice as quickly utilized for ketone body production than palmitate and oleate were. As concluded from the 'crossover' plot the inhibitory effect of fatty acids on gluconeogenesis in rabbit kidney tubules may be due to: (i) a decrease of mitochondrial generation of phosphoenolpyruvate and (ii) an inhibition of flux through fructose-1,6-bisphosphatase.