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Growth-regulatory effects of glucagon, insulin, and epidermal growth factor in cultured hepatocytes

Temporal aspects and evidence for bidirectional control by cyclic AMP

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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.

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Author notes

  1. Tor-Erik Sand

    Present address: Department of Surgery, Aker Hospital, N-0514, Oslo 5, Norway

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, University of Oslo, Blindern, P.O. Box 1057, N-0316, Oslo, Norway

    Tor-Erik Sand, G. Hege Thoresen, Magne Refsnes & Thoralf Christoffersen

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  1. Tor-Erik Sand
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Supported by grants from The Norwegian Cancer Society, The Nordic Insulin Fund, and The Norwegian Council for Science and the Humanities.

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Sand, TE., Thoresen, G.H., Refsnes, M. et al. Growth-regulatory effects of glucagon, insulin, and epidermal growth factor in cultured hepatocytes. Digest Dis Sci 37, 84–92 (1992). https://doi.org/10.1007/BF01308347

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  • DOI: https://doi.org/10.1007/BF01308347

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