Glucocorticoids increase insulin binding and the amount of insulin-receptor mRNA in human cultured lymphocytes.
The effect of steroid hormones on insulin binding and the amount of insulin-receptor mRNA was examined in IM-9 lymphocytes. Cortisol and cortexolone, but not oestrogen, increased both the binding of insulin and the amount of insulin-receptor mRNA in a time- and dose-dependent manner. Cortisol was most potent, and induced a 2-fold increase in insulin binding and a 4-fold increase in mRNA. The elevation in binding was due to an increased number of insulin receptors at the cell surface. The increase in mRNA involved all four of the insulin-receptor mRNAs and could not be inhibited by cycloheximide. The cortisol-induced increase in mRNA was associated with a 3-4-fold increase in the synthesis of pro-receptor. The relative potency of the three steroids indicated that these effects were mediated by an interaction with the glucocorticoid receptor. The results of this study suggest that cortisol can increase the number of insulin receptors at the cell surface by increasing the amounts of insulin-receptor mRNA and the synthesis de novo of insulin receptors.
Shibasaki
Y
Y
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Sakura
H
H
Odawara
M
M
Shibuya
M
M
Kanazawa
Y
Y
Akanuma
Y
Y
Takaku
F
F
Kasuga
M
M
D015065:17-Hydroxycorticosteroids / Q000494:pharmacology*; D002460:Cell Line; D003350:Cortodoxone / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*
D015065:17-Hydroxycorticosteroids; D007328:Insulin; D012333:RNA, Messenger; D004958:Estradiol; D003513:Cycloheximide; D011972:Receptor, Insulin; D003350:Cortodoxone; D006854:Hydrocortisone