Glucose homeostasis changes and pancreatic β-cell proliferation after switching to cyclosporin in tacrolimus-induced diabetes mellitus

Rodríguez-Rodríguez, Ana Elena; Triñanes, Javier; Porrini, Esteban; Velázquez-García, Silvia; Fumero, Cecilia; Vega-Prieto, María Jose; Díez-Fuentes, María Luisa; Lima, Sergio Luis; Salido, Eduardo; Torres, Armando

doi:http://dx.doi.org/10.1016/j.nefroe.2015.06.006

Glucose homeostasis changes and pancreatic β-cell proliferation after switching to cyclosporin in tacrolimus-induced diabetes mellitus

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Rodríguez-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.2015.06.006

Abstract

Background. 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.