Epidermal growth factor administration decreases liver glycogen and causes mild hyperglycaemia in mice.
Several laboratories report different effects of epidermal growth factor (EGF) on glycogen metabolism in hepatocytes. The discrepancies may be attributed to differences in the experimental conditions. It is therefore important to establish the actual effect of EGF in vivo. Because large physiological variations of EGF concentration in plasma occur in mice, we used this species to address this question. In freshly isolated mouse hepatocytes, EGF increased glycogen degradation in a dose-dependent manner. The maximal effect (36% increase over basal glycogenolysis) was smaller than maximal effects of classical glycogenolytic hormones like adrenaline or glucagon (more than 150% increase over basal). This is in keeping with the smaller effect of EGF on phosphorylase a activity. In contrast with these hormones, EGF did not inhibit glycolysis. Thus these effects of EGF in mouse hepatocytes are similar to those recently described by us in rat hepatocytes [Quintana, Grau, Moreno, Soler, Ramirez and Soley (1995) Biochem J 308, 889-894]. When administered to whole animals, EGF increased phosphorylase a activity, decreased the glycogen content in the liver and caused mild hyperglycaemia. Taking together the results obtained for isolated cells and for whole animals, we suggest that the glucosyl residues released from glycogen are used mostly by the liver rather than released to the circulation. This would be different from the action of the classical glycogenolytic hormones, adrenaline and glucagon.
Grau
M
M
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
Tebar
F
F
Ramírez
I
I
Soley
M
M
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D006943:Hyperglycemia / Q000139:chemically induced*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D051379:Mice
D001786:Blood Glucose; D008112:Liver Glycogen; D004815:Epidermal Growth Factor; D005934:Glucagon; D004837:Epinephrine