The Effect of Glucocorticoids on the Insulin Receptor: An in Vivo and inVitro Study

Abstract

We have studied the effect of glucocorticoid exposure on the insulin receptor of short term cultures of human lymphocytes (IM-9 cells) and the effect of short term administration of these agents to normal volunteers. When cultured human lymphocytes were exposed to lO^-5 M hydrocortisone for 18 h at 37 C, insulin binding increased due to an increase in the number of receptors per cell. The effect had appropriate specificity in terms of concentration and type of steroid used. By contrast, hGH binding to these cells was decreased under similar circumstances of incubation, due to a decrease in the number of hGH receptors per cell. When prednisone (40 mg/day) was given to normal subjects for 3 days, a moderate state of insulin resistance was induced characterized by a modest increase in blood glucose and a more pronounced increase in plasma insulin concentration. Under these circumstances there was no change in tracer insulin binding to peripheral monocytes nor changes in the concentration of insulin necessary to inhibit binding by 50%, the number of receptors per cell or the affinity of the receptor. We conclude that glucocorticoids increase insulin binding in vitro in cultured human lymphocytes but that competing influences in vivo such as increasing circulating insulin concentration, redistribution of cell types in the circulation, and possibly other influences prevent these changes from occurring in circulating monocytes. These findings emphasize the complexity of studying the effects of pharmacological agents on hormone binding.