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

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  • dc.contributor.author Rodríguez-Rodríguez, Ana Elena
  • dc.contributor.author Triñanes, Javier
  • dc.contributor.author Porrini, Esteban
  • dc.contributor.author Velázquez-García, Silvia
  • dc.contributor.author Fumero, Cecilia
  • dc.contributor.author Vega-Prieto, María Jose
  • dc.contributor.author Díez-Fuentes, María Luisa
  • dc.contributor.author Lima, Sergio Luis
  • dc.contributor.author Salido, Eduardo
  • dc.contributor.author Torres, Armando
  • dc.date.accessioned 2024-12-09T07:24:53Z
  • dc.date.available 2024-12-09T07:24:53Z
  • dc.date.issued 2015
  • dc.description.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.
  • dc.description.sponsorship The authors would like to thank the project IMBRAIN (FP7-RE6-POT-2012-CT2012-316137-IMBRAIN), founded under the 7° Frameworks Programme. They thank the Instituto de Salud Carlos III (Health Investment Fund: HIF) for the following financing: PI 07/0732, REDINREN RD/0021/0008 and PI10/02428. They also give their acknowledgements to the funds of IRSIN (Instituto Reina Sofía de Investigación) and to Funds FEDER.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation 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
  • dc.identifier.doi http://dx.doi.org/10.1016/j.nefroe.2015.06.006
  • dc.identifier.issn 2013-2514
  • dc.identifier.uri http://hdl.handle.net/10230/68942
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Nefrología (English Edition). 2015 May-Jun;35(3):264-72
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/316137
  • dc.rights © 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/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword Post-transplant diabetes mellitus
  • dc.subject.keyword Tacrolimus
  • dc.subject.keyword Cyclosporin A
  • dc.title Glucose homeostasis changes and pancreatic β-cell proliferation after switching to cyclosporin in tacrolimus-induced diabetes mellitus
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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