Control of glycolysis and lipogenesis in the liver by glucagon at the phosphofructokinase-fructose 1,6-diphosphatase site

We have examined the effects of glucagon on lipogenesis from fasted-refed rats incubated under two conditions, either without added substrate or with 10 mml-lactate. Net glycolysis (from glycogen) occurs in the absence of glucagon. This glycolysis is inhibited by glucagon under conditions of no added lactate, and reversed by glucagon to a net gluconeogenesis in the presence of 10 mm lactate. Glucagon markedly inhibits fatty acid synthesis (estimated by incorporation of tritium from THO) in hepatocytes incubated without added substrate; but, in the presence of 10 mml-lactate, the inhibition of fatty acid synthesis is only about 10%. The inhibition of lipogenesis from endogenous glycogen is primarily caused by inhibition of glycolysis. Glucagon markedly lowers the $\text{C}\text{-4,5,6}\text{C}\text{-1,2,3}$ ratio in glucose produced from 1-¹⁴C]galactose, indicating a strong inhibition of phosphofructokinase flux. The $\text{C}\text{-1,2,3}\text{C}\text{-4,5,6}$ ratio in glucose from 1-¹⁴C]glycerol is only slightly less than 1, indicating an active fructose diphosphatase flux even under conditions of active net glycolysis. Glucagon increases this ratio only slightly, suggesting that an acute increase of fructose diphosphatase activity by glucagon may occur, but is of much less importance than the decrease of phosphofructokinase.