The molecular pathogenesis of post-transplantation diabetes mellitus induced by calcineurin inhibitors

Calcineurin Inhibitors(CNIs) are sort of medicine that inhibits calcineurin in order to suppress immunologic system,representing by FK506 and CsA.Many studies demonstrate that CNIs are at greater risk of post-transplantation diabetes mellitus(PTDM) while making effect on suppression of immunologic system.Its pathogenesis is mainly associated with inhibition of calcineurin.CNIs inhibit calcineurin,the activator of cytosolic nuclear factor of activated T cells 1(NFATc1) in beta-cell,which result in an absolute deficiency in beta-cell mass and insulin.In high glucose,transducer of regulated CREB activity 2(TORC2) is continuously phosphorylated,on the basis of inhibition of calcineurin,which prevents TORC2 dephosphorylation,nuclear entry and cAMP response element binding protein(CREB) activation,leading to PTDM.Furthermore,the studies find more FK506-binding protein(FKBP-12)in beta-cell,which result in congregation of FK506.But there is no evidence to show the same rule with CsA.It can explain why FK506 is more diabetogenic than CsA.