title: Glucose homeostasis changes and pancreatic β-cell proliferation after switching to cyclosporin in tacrolimus-induced diabetes mellitus.
abstract: BACKGROUND
  Switching to cyclosporine 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 (0.3mg/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 (2.5mg/kg/day) for 5 days (tacrolimus-cyclosporin). An additional cohort of 22 obese Zucker rats received the vehicle for 17 days and were 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.
  
  
  CONCLUSIONS
  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.
authors: Unidad de Investigación, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, España.
authors: Ana Elena
authors: AE
authors: Rodríguez-Rodríguez
authors: Unidad de Investigación, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, España.
authors: Javier
authors: J
authors: Triñanes
authors: Unidad de Investigación, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, España. Electronic address: estebanporrini72@hotmail.com.
authors: Esteban
authors: E
authors: Porrini
authors: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, España.
authors: Silvia
authors: S
authors: Velázquez-García
authors: Unidad de Investigación, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, España.
authors: Cecilia
authors: C
authors: Fumero
authors: Laboratorio central, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, España.
authors: María Jose
authors: MJ
authors: Vega-Prieto
authors: Laboratorio central, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, España.
authors: María Luisa
authors: ML
authors: Díez-Fuentes
authors: Unidad de Investigación, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, España.
authors: Sergio
authors: S
authors: Luis Lima
authors: Centro para la Investigación Biomédica de Canarias, Universidad de La Laguna, San Cristóbal de La Laguna, Santa Cruz de Tenerife, España.
authors: Eduardo
authors: E
authors: Salido
authors: Servicio de Nefrología, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, España.
authors: Armando
authors: A
authors: Torres
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D065095:Calcineurin Inhibitors / Q000494:pharmacology / Q000633:toxicity*; D050260:Carbohydrate Metabolism / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D057915:Drug Substitution; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000187:drug effects; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects*; D009765:Obesity / Q000150:complications / Q000378:metabolism; D011384:Proinsulin / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011924:Rats, Zucker; D016559:Tacrolimus / Q000633:toxicity*
chemical_list: D065095:Calcineurin Inhibitors; D016572:Cyclosporine; D011384:Proinsulin; D005947:Glucose; D016559:Tacrolimus
keywords: Ciclosporina-A; Cyclosporin A; Diabetes postrasplante; Post-transplant diabetes mellitus; Tacrolimus