Deciphering tacrolimus-induced toxicity in pancreatic ß-cells.
Date
2017Abstract
b Cell transcription factors such as fork head box proteinO1(FoxO1), v-maf musculoaponeurotic fibrosarcoma oncogene homologA (MafA), pancreatic and duodenal homeobox1, and neuronal differentiation 1, are dysfunctional in type 2 diabetes mellitus (T2DM). Posttransplant diabetes mellitus resembles T2DMandreflectsinteractionbetweenpretransplant insulin resistanceand immunosuppressants ,mainly calcineurininhibitors(CNIs).We evaluated the effect of tacrolimus(TAC),cyclosporineA(CsA),and metabolic stressors (glucose plus palmitate) on insulinomab cells invitro and in pancreata of obeseand lean Zucker rats.Cellswereculturedfor5dayswith 100lMpalmitateand22mMglucose;CsA(250ng/ mL)orTAC(15ng/mL)were added in the last48h.