Actions of quercetin on gluconeogenesis and glycolysis in rat liver.

1. The action of quercetin on glucose catabolism and production was investigated in the perfused rat liver. 2. Quercetin inhibited lactate production from glucose: 80% inhibition was found at a quercetin concentration of 100 micro M, and at higher concentrations inhibition was complete. 3. Pyruvate production from glucose presented a complex pattern, but stimulation was evident at 100 and 300 micro M quercetin. Oxygen uptake tended to be increased. 4. Glucose synthesis from lactate and pyruvate was inhibited. Inhibition was already evident at 50 micro M quercetin and almost complete at 300 micro M. Concomitantly, the increment in oxygen uptake caused by lactate plus pyruvate was stimulated by 50 micro M quercetin, but clearly inhibited by higher concentrations (100-500 micro M). 5. Glucose phosphorylation in the high-speed supernatant fractions of liver homogenates was inhibited by quercetin, but only at concentrations above 150 micro M. 6. It is concluded that quercetin can inhibit both glucose degradation and production and increase the cytosolic NAD(+)/NADH ratio. 7. These effects are likely to arise from many causes. Reduction of oxidative phosphorylation, inhibition of Na(+)-K(+)-ATPase, inhibition of glucokinase and inhibition of glucose 6-phosphatase could all contribute to the overall action of quercetin.