Rapamycin (sirolimus) is a macrolide fungicide with immunosuppressant properties that is used in human islet transplantation. Little is known about the effects of rapamycin on MIN-6 cells and islets. Rapamycin had a dose-dependent, time-dependent, and glucose-independent deleterious effect on MIN-6 cell viability. At day 1, using the MTT method, 0.01 nmol/l rapamycin reduced cell viability to 83 +/- 6% of control (P < 0.05). Using the calcein AM method, at day 2, 10 nmol/l rapamycin caused a reduction in cell viability to 73 +/- 5% of control (P < 0.001). Furthermore, 10 and 100 nmol/l rapamycin caused apoptosis in MIN-6 cells as assessed by the transferase-mediated dUTP nick-end labeling assay. Compared with control, there was a 3.1 +/- 0.6-fold increase (P < 0.01) in apoptosis in MIN-6 cells treated with 10 nmol/l rapamycin. A supra-therapeutic rapamycin concentration of 100 nmol/l significantly impaired glucose- and carbachol-stimulated insulin secretion in rat islets and had a deleterious effect on the viability of rat and human islets, causing apoptosis of both alpha- and beta-cells.
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