Effect of cyclosporine on insulin binding to erythrocytes in type 1 diabetes mellitus of recent onset.
The effect of cyclosporine (Cyclosporin A) on insulin binding to erythrocytes was investigated in Type 1 diabetes mellitus of recent onset. The subjects were drawn from a pilot study (The Canadian Open Study on the effects of immunosuppression with Cyclosporine in Type 1 Diabetes Mellitus) in which 50% of the patients demonstrated remission during one year of cyclosporine administration. Specific binding of 125I-insulin was examined before and after 3, 6, or 12 months of cyclosporine in different groups of patients. Those who maintained target control of blood glucose without exogenous insulin for two or more weeks were designated non-insulin requiring. Basal and intravenous glucagon-stimulated immunoreactive plasma C-peptide rose in all groups but to higher levels in non-insulin requiring groups. Insulin binding at tracer concentration, reflecting the number of insulin receptors, was initially normal but tended to decrease with duration of cyclosporine administration. This decrease was significant especially in groups which remained insulin-requiring throughout the study. The affinity of erythrocyte receptors was assessed by determining the insulin concentration required for 50% inhibition of 125I-insulin binding, the ID50. These values suggested that the affinity of insulin receptors was not affected in subjects attaining non-insulin requiring remission; however, in subjects remaining dependent on exogenous insulin, receptor affinity appeared to be adversely affected. Even in subjects who demonstrated complete remission, affinity was decreased during periods of dependence on exogenous insulin. After discontinuation of cyclosporine for one month or more, the mean daily insulin dosage increased and plasma C-peptide decreased. Insulin binding at tracer concentration was not affected but the apparent affinity was decreased after withdrawal of cyclosporine. These results suggest that insulin action at the receptor may be affected by the administration of cyclosporine. The number of insulin receptors appears to be decreased but whether this effect has an impact on insulin sensitivity remains to be seen. Receptor affinity appears to be affected mainly by exogenous insulin. Thus immunosuppression with cyclosporine in newly diagnosed Type 1 diabetes mellitus may have a modest adverse effect on insulin receptors; whether the benefits of cyclosporine treatment outweigh this risk is difficult to assess.
Behme
M T
MT
Department of Medicine, University of Western Ontario, London, Canada.
Dupre
J
J
Stiller
C R
CR
D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*
D007328:Insulin