Epidermal growth factor counteracts the glycogenic effect of insulin in parenchymal hepatocyte cultures.
Rat parenchymal hepatocytes in monolayer culture were used to study the metabolic effects of epidermal growth factor (EGF) and insulin on ketogenesis, gluconeogenesis and glycogen metabolism. EGF, unlike insulin, did not inhibit ketogenesis from palmitate or gluconeogenesis from pyruvate in hepatocyte cultures. It also had no effect on these pathways in the presence of insulin. In contrast, EGF potently counteracted the stimulation of [14C]pyruvate incorporation into glycogen by insulin, and also glycogen deposition from both gluconeogenic precursors and glucose. The EGF concentration causing half-maximal effect was about 0.1 nM. The anti-glycogenic effect of EGF was observed after both long-term (24 h) and short-term (1 h) exposure to EGF, and was more marked in the presence of insulin than in its absence. EGF did not displace bound insulin, suggesting that it neither competes for the insulin receptor nor affects the affinity of the receptor for insulin. EGF did not alter cellular cyclic AMP; and inhibition of cyclic AMP phosphodiesterase activity did not prevent the anti-glycogenic effect of EGF. In liver-derived dividing epithelial cells, Hep-G2 cells and fibroblasts, which have no capacity for gluconeogenesis, EGF did not counteract the stimulatory effect of insulin on [14C]glucose incorporation into glycogen, and in the epithelial cells EGF increased [14C]glucose incorporation into glycogen. The counter-effect of EGF on the glycogenic action of insulin in parenchymal hepatocytes may be due to a direct effect on glycogen metabolism or to an interaction with the post-receptor events in insulin action.
Chowdhury
M H
MH
Department of Medicine, Medical School, University of Newcastle upon Tyne, U.K.
Agius
L
L
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007329:Insulin Antagonists; D007657:Ketone Bodies / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000096:biosynthesis*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D007329:Insulin Antagonists; D007657:Ketone Bodies; D008112:Liver Glycogen; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D005954:Glucosephosphate Dehydrogenase; D015105:3',5'-Cyclic-AMP Phosphodiesterases