Rodríguez-Rodríguez, Ana ElenaTriñanes, JavierPorrini, EstebanVelázquez-García, SilviaFumero, CeciliaVega-Prieto, María JoseDíez-Fuentes, María LuisaLima, Sergio LuisSalido, EduardoTorres, Armando2024-12-092024-12-092015Rodríguez-Rodríguez AE, Triñanes J, Porrini E, Velázquez-García S, Fumero C, Vega-Prieto MJ, et al. Glucose homeostasis changes and pancreatic β-cell proliferation after switching to cyclosporin in tacrolimus-induced diabetes mellitus. Nefrología (English Edition). 2015 May-Jun;35(3):264-72. DOI: 10.1016/j.nefroe.2015.06.0062013-2514http://hdl.handle.net/10230/68942Background. Switching to cyclosporin A may result in a reversion of tacrolimus-induced diabetes mellitus. However, mechanisms underlying such a reversion are still unknown. Methods. 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. Results. 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. Conclusion. 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.application/pdfeng© 2015 The Authors. Published by Elsevier España, S.L.U. on behalf of Sociedad Española de Nefrología. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.nefroe.2015.06.006Post-transplant diabetes mellitusTacrolimusCyclosporin Ainfo:eu-repo/semantics/openAccess