Enhanced insulin stimulation of sugar transport and DNA synthesis by glucocorticoids in cultured human skin fibroblasts

• Published in: Archives of biochemistry and biophysics Vol. 226; no. 2; pp. 498 - 505
• Main Authors: Germinario, Ralph J., McQuillan, Angela, Oliveira, Maureen, Manuel, Susannia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.10.1983
• Subjects: Biological Transport, Active - drug effects; Cells, Cultured; Deoxy Sugars - metabolism; Deoxyglucose - metabolism; Dexamethasone - pharmacology; DNA Replication - drug effects; Drug Synergism; Fibroblasts - drug effects; Fibroblasts - metabolism; Humans; Hydrocortisone - pharmacology; Insulin - pharmacology; Kinetics; Skin - drug effects; Skin - metabolism
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/0003-9861(83)90319-3

Glucocorticoids will enhance the growth of cultured human skin fibroblasts in serum-containing medium. In serum-free cultures hydrocortisone (5 × 10 −6 m) will enhance insulin stimulation of sugar transport and DNA synthesis (as measured by thymidine incorporation into trichloroacetic acid-precipitable material). The optimal concentration for the glucocorticoid effect on DNA synthesis was 5 × 10 −8 m for dexamethasone and 5 × 10 −7 m for hydrocortisone. In dexamethasone-treated cells, concentrations of insulin as low as 250 μU/ml (10 ng/ml) were effective in stimulating DNA synthesis. Further, hydrocortisone and dexamethasone (both at 5 × 10 −6 m) exhibited potentiating effects on insulin-stimulated sugar transport. These effects appeared to be mediated via inhibitory actions on the hexose transport system with the preservation of a functional insulin-receptor interaction resulting in insulin stimulation of deoxy- d-glucose transport at physiological insulin concentrations, 250 μU/ml (10 ng/ml). Hydrocortisone also enhanced specific [ 125I]insulin binding in these cells. The data indicate that the mechanism(s) of glucocorticoid enhancement of two actions of insulin may be different.