Cyclosporin-induced inhibition of insulin secretion in isolated rat islets and HIT cells.
The effects of cyclosporin, an immunosuppressive agent used in diabetic and nondiabetic patients, on in vitro glucose-induced insulin secretion were evaluated in isolated islets and in a glucose-responsive clonal beta-cell line (HIT cells). Cyclosporin inhibited glucose-induced insulin secretion in a dose-response manner at concentrations commonly found in human blood. With isolated islets, four time periods (0-5, 5-15, 15-30, and 30-60 min) were examined after stimulation with 300 mg/dl glucose. Inhibition of insulin secretion by cyclosporin was evident by 5-15 min as well as during later times with progressively smaller drug concentrations. With HIT cells, longer-term effects were examined after 16 h of incubation with various drug concentrations. Inhibition of insulin secretion was again observed, and these inhibitory effects were not reversed by drug washout. A cyclosporin concentration of 0.1 microgram/ml, which is a therapeutic blood level in humans, was sufficient to inhibit insulin secretion in both in vitro models. Patients using this drug should be carefully monitored for signs of deficient insulin secretion.
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003524:Cyclosporins / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008647:Mesocricetus; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins; D007328:Insulin; D005947:Glucose