THE EARLY STIMULATION OF GLYCOLYSIS BY EPIDERMAL GROWTH-FACTOR IN ISOLATED RAT HEPATOCYTES IS SECONDARY TO THE GLYCOGENOLYTIC EFFECT

We have studied the relationship between the effect of epidermal growt h factor (EGF) on glycogen metabolism and its effect on glycolysis, in rat hepatocyte suspensions. Although 10 nM glucagon or 10 mu M adrena line increased glycogen degradation by more than 120%, 10 nM EGF incre ased glycogenolysis by less than 20 % in hepatocytes incubated in gluc ose-free medium. Both glucagon and adrenaline increased phosphorylase a activity by more than 130 %; EGF increased this activity by about 30 %. Under basal conditions, 65% of the glucosyl residues were released as free glucose and about 30 % ended up as C-3 molecules (lactate and pyruvate). Both glucagon and adrenaline decreased the proportion of g lucosyl units that rendered glycolysis endproducts (to 2% for glucagon and 6% for adrenaline) and increased the proportion that ended up as free glucose (to 94% and 88 % of the glucosyl residues for glucagon an d adrenaline respectively). EGF increased the production of both free glucose and lactate+pyruvate, but the proportion of glucosyl residues that ended up as free glucose or glycolysis end-products was unchanged . In glycogen-depleted hepatocytes incubated in the presence of 25 mM glucose, EGF affected neither glycogen deposition nor glycolysis. EGF increased cytosolic free Ca2+, and neomycin decreased both the Ca2+ si gnal and the glycogenolytic effect. In conclusion, our results indicat e that the effect of EGF on glycolysis is secondary to the Ca2+-mediat ed stimulation of glycogenolysis in rat hepatocyte suspensions.