Glucocorticoids Regulate Insulin Binding in a Rat Glial Cell Line*

Abstract

We have examined insulin receptor regulation by glucocorticoids in the C6 rat glioma cell line. Dexamethasone decreased insulin binding to intact cell monolayers in a dose and time-dependent fashion. The effect is maximal between 48 and 72 h with 50 nM dexamethasone that decreased binding by 40-60%. The natural steroid corticosterone produced a similar effect although it was less potent, and the antiglucocorticoid 17 alpha-methyltestosterone was ineffective in lowering the receptor and partially antagonized the effect of dexamethasone. Total number of binding sites was decreased by glucocorticoids, and when analyzed with a two-site model a 3-fold increase in the dissociation constant (Kd) of the low affinity site was also observed. In the absence of protein synthesis the receptor accumulates at the cell surface, since cycloheximide produced a large increase of insulin binding. Cycloheximide totally blocked the effect of dexamethasone when both compounds were added together to the cells suggesting that protein synthesis is necessary for the effect of the glucocorticoid. By contrast, in cells pretreated with dexamethasone, cycloheximide was unable to produce an increase in cell surface receptor, showing that glucocorticoids probably deplete not only membrane receptor but also total cellular receptor.

Enhanced Brain Cell Proliferation Following Early Adrenalectomy in Rats

“…It is also possible that glucocorticoids alter the synthesis or action of various mitogenic factors (Herschman, 1986). For example, Montiel et al (1987) recently reported that glucocor-ticoids, at doses that suppress proliferation of cultured C6 glioma cells, also reduce insulin receptor binding. As progress continues in identifying the factors responsible for regulating brain cell proliferation in vivo, it will be important to determine whether these factors are subject to modulation by glucocorticoid hormones.…”

Dexamethasone effects on creatine kinase activity and insulin‐like growth factor receptors in cultured muscle cells

“…Dexamethasone treatment of muscle cells has been reported to alter enzyme levels, cell proliferation, and heterologous hormone receptor binding in a variety of cell types (Max et al, 1987;Florini, 1979, 1980;McGrath and Goldspink, 1982;Smith et al, 1981;Kahn et al, 1978;de Pirro et al, 1980;Grunfeld et al, 1981;Montiel et al, 1987;Fantus et al, 1982). For example, in vivo and in vitro studies indicated that glucocorticoids modulate tissue-dependent insulin responses (Kahn et al, 1978;de Pirro et al, 1980;Goldfine et al, 1973;Car0 and Amatruda, 1982;Fantus et al, 1982;Salhanick et al, 1983;Grunfeld et al, 1981;Montiel et al, 1987). In lymphocytes (Fantus et al, 1982) and hepatocytes (Caro and Amatruda, 1982;Salhanick et al, 1983) insulin receptors were found to be up-regulated by glucocorticoids, whereas fibroblasts (Grunfeld et al, 1981) and glial cells (Mon-tie1 et al, 1987) exhibited reduced insulin binding.…”

Dexamethasone pretreatment of rat insulinoma cells decreases binding of glucagon-like peptide-1(7–36)amide

“…It is believed that the binding of corticosteroids to receptors of a target cell, or a modification of the phospholipid structure of membranes by corticosteroids, can regulate binding of another hormone to the same cell, and thereby modulate the biological response to this second hormone (Nelson, 1980). However, in some cases it has been speculated that steroids may influence receptor turnover (Montiel, Ortiz-Caro, Villa et al 1987). It was therefore of interest to investi¬ gate the effect of dexamethasone on the action of GLPl(7-36)amide in RINm5F cells.…”