Glucose homeostasis changes and pancreatic β-cell proliferation after switching to cyclosporin in tacrolimus-induced diabetes mellitus
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 rece...
| Autores: | , , , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2015 |
| País: | España |
| Recursos: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/68942 |
| Acesso em linha: | http://hdl.handle.net/10230/68942 http://dx.doi.org/10.1016/j.nefroe.2015.06.006 |
| Access Level: | acceso abierto |
| Palavra-chave: | Post-transplant diabetes mellitus Tacrolimus Cyclosporin A |
| Resumo: | 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. |
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