Inhibitory effects of immunosuppressive drugs on insulin secretion from HIT-T15 cells and Wistar rat islets

Transplantation
B W PatyR P Robertson

Abstract

Until recently, islet allotransplantation for type 1 diabetic patients has been largely unsuccessful. Previous pharmacologic studies of single drugs have suggested that one factor contributing to this poor success is toxicity of immunosuppressive drugs on transplanted islets. However, no comprehensive study of agents currently used for islet transplantation has been previously reported. Consequently, we exposed HIT-T15 cells and Wistar rat islets to various concentrations of five immunosuppressive agents for 48 and 24 hr, respectively, and measured glucose-stimulated insulin secretion during subsequent static incubations. Results are expressed as percent reduction of insulin secretion at the lower and upper limits, respectively, of plasma drug concentrations used in clinical transplantation compared with control (no drug exposure). Insulin secretion from HIT-T15 cells was significantly inhibited by 74% and 90% after exposure to methylprednisolone (P<0.05), 11% and 24% after exposure to cyclosporine (P<0.01), 60% and 83% after exposure to mycophenolate (P<0.05), 56% and 63% after exposure to sirolimus (P<0.001), and 10% and 20% after exposure to tacrolimus (P<0.001). Insulin secretion from Wistar rat islets was reduced by 0% and...Continue Reading

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