title: Growth-regulatory effects of glucagon, insulin, and epidermal growth factor in cultured hepatocytes. Temporal aspects and evidence for bidirectional control by cyclic AMP.
abstract: Data presented indicate that in hepatocytes insulin and glucagon promote growth by acting in a relatively early part of the prereplicative period (G0 or early G1) whereas cells (if pretreated with insulin) become more sensitive to EGF at the later stages, ie, nearer the S phase entry. The data indicate that at least two effects of glucagon (cAMP) on hepatocyte proliferation exist; in addition to a growth-promoting modulation early in the prereplicative period, there is also an inhibitory effect of glucagon (as well as other cAMP-elevating agents) that is exerted at a point shortly before the G1-to-S transition. Because both effects occur dose-dependently in the normal range of glucagon concentrations in portal blood, it is conceivable that glucagon/cAMP is involved both when liver growth is initiated and terminated.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Oslo, Norway.
authors.forename: T E
authors.initials: TE
authors.lastname: Sand
authors.forename: G H
authors.initials: GH
authors.lastname: Thoresen
authors.forename: M
authors.initials: M
authors.lastname: Refsnes
authors.forename: T
authors.initials: T
authors.lastname: Christoffersen
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000166:cytology*; D016196:S Phase; D013997:Time Factors
chemical_list: D007328:Insulin; D004815:Epidermal Growth Factor; D004247:DNA; D005934:Glucagon; D000242:Cyclic AMP