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Interaction of insulin, glucocorticoids, and protein kinase C in the regulation of insulin‐like growth factor‐binding protein‐1 production by H4IIE rat hepatoma cells
Author(s) -
Lewitt Moira S.,
Saunders Heather,
Baxter Robert C.
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199601)166:1<121::aid-jcp14>3.0.co;2-i
Subject(s) - insulin , protein kinase a , medicine , growth factor , binding protein , insulin like growth factor binding protein , endocrinology , insulin like growth factor , grb10 , kinase , chemistry , microbiology and biotechnology , biology , insulin receptor , insulin resistance , biochemistry , receptor , gene
A sensitive RIA was used to examine regulation of IGFBP‐1 in H4IIE rat hepatoma cells. IGFBP‐1 was stimulated up to tenfold by dexamethasone and corticosterone, and this stimulation was abolished by RU486. The effect of dexamethasone increased with time in culture. Phorbol 12‐myristate 13‐acetate (PMA) stimulated IGFBP‐1 up to fourfold with a maximal effect in short‐term culture. Dexamethasone and PMA were additive in stimulating IGFBP‐1. Under basal conditions IGFBP‐1 production was linearly related to cell density: however, stimulation by dexamethasone was greatest in confluent cells, and PMA had a greater effect in sparse cultures. Insulin inhibited IGFBP‐1 up to 80%, and this effect diminished with time in culture but was unaffected by cell density. Dexamethasone was stimulatory in the presence of a maximal inhibitory concentration of insulin, and insulin was inhibitory in the presence of maximal dexamethasone from 3–48 h in culture, regardless of cell density. PMA abolished the inhibitory action of insulin on IGFBP‐1 secretion and mRNA expression during incubation periods of less than 4 h and not during longer incubations. PMA did not influence the stability of IGFBP‐1 mRNA. We conclude that, in rat H4IIE cells, dexamethasone and PMA stimulate IGFBP‐1 by independent mechanisms and speculate that when protein kinase C is activated the inhibitory action of insulin is blocked. © 1996 Wiley‐Liss, Inc.