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• W4256231856 abstract "Switching to cyclosporin A may result in a reversion of tacrolimus-induced diabetes mellitus. However, mechanisms underlying such a reversion are still unknown. Obese Zucker rats were used as a model for tacrolimus-induced diabetes mellitus. A cohort of 44 obese Zucker rats received tacrolimus for 11 days (0.3 mg/kg/day) until diabetes development; then, (a) 22 rats were euthanized at day 12 and were used as a reference group (tacrolimus-day 12), and (b) 22 rats on tacrolimus were shifted to cyclosporin (2.5 mg/kg/day) for 5 days (tacrolimus-cyclosporin). An additional cohort of 22 obese Zucker rats received the vehicle for 17 days and was used as a control group. All animals underwent an intraperitoneal glucose tolerance test at the end of the study. β-Cell proliferation, apoptosis and Ins2 gene expression were evaluated. Compared to rats in tacrolimus-day 12 group, those in tacrolimus-cyclosporin group showed a significant improvement in blood glucose levels in all assessment points in intraperitoneal glucose tolerance test. Diabetes decreased from 100% in tacrolimus-day-12 group to 50% in tacrolimus-cyclosporin group. Compared to tacrolimus-day-12 group, rats in tacrolimus-cyclosporin group showed an increased β-cell proliferation, but such an increase was lower than in rats receiving the vehicle. Ins2 gene expressions in rats receiving tacrolimus-cyclosporin and rats receiving the vehicle were comparable. An early switch from tacrolimus to cyclosporin in tacrolimus-induced diabetes mellitus resulted in an increased β-cell proliferation and reversion of diabetes in 50% of cases. El cambio a ciclosporina A podría revertir la diabetes inducida por tacrolimus. Sin embargo, los mecanismos de esta reversibilidad se desconocen. Usamos como modelo de diabetes inducida por tacrolimus las ratas Zucker obesas. Un grupo de 44 ratas Zucker obesas fue tratado con tacrolimus durante 11 días (0,3 mg/kg/día) hasta que desarrollaron diabetes; posteriormente, a) 22 fueron sacrificadas a día 12 como grupo referencia (tacrolimus-d12), y b) en otras 22 el tacrolimus fue reemplazado por ciclosporina (2,5 mg/kg/día) durante 5 días (tacrolimus-ciclosporina). Veintidós ratas Zucker obesas recibieron vehículo durante 17 días (grupo control). A todos los animales se les realizó una sobrecarga intraperitoneal de glucosa al final del experimento. Se analizó la proliferación de la célula β, la apoptosis y la expresión del gen Ins2. En el grupo tacrolimus-ciclosporina, los niveles de glucemia mejoraron significativamente en cada punto del test intraperitoneal de glucosa comparados con el grupo tacrolimus-d12. La diabetes se redujo del 100% en los tacrolimus-d12 hasta el 50% en tacrolimus-ciclosporina. La proliferación de las células β en tacrolimus-ciclosporina se incrementó en comparación con tacrolimus-d12, pero fue menor que en los tratados con vehículo. La expresión génica de Ins2 en tacrolimus-ciclosporina fue comparable a los tratados con el vehículo. El cambio temprano de tacrolimus por ciclosporina en la diabetes inducida por tacrolimus incrementa la proliferación de la célula β y revierte la diabetes en un 50% de los casos." @default.
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• W4256231856 date "2015-05-01" @default.
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• W4256231856 title "Glucose homeostasis changes and pancreatic β-cell proliferation after switching to cyclosporin in tacrolimus-induced diabetes mellitus" @default.
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• W4256231856 doi "https://doi.org/10.1016/j.nefroe.2015.06.006" @default.
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