Differential effects of voclosporin and tacrolimus on insulin secretion from human islets

The incidence of new onset diabetes after transplant (NODAT) has increased over the past decade, likely due to calcineurin inhibitor-based immunosuppressants, including tacrolimus (TAC) and cyclosporin (CsA). Voclosporin (VCS), a next generation calcineurin inhibitor is reported to cause fewer incidences of NODAT but the reason is unclear. Whilst calcineurin signaling plays important roles in pancreatic beta-cell survival, proliferation, and function, its effects on human beta-cells remain understudied. In particular, we do not understand why some calcineurin inhibitors have more profound effects on the incidence of NODAT. Here, we compared the the effects of TAC and VCS on the transcriptomic profile of human islets. Overall design: There are 3 conditions. Groups of 200 islets from 7 independent donors were treated for 48 hours with vehicle (DMSO), TAC (30 ng/ml) or VCS (60 ng/ml) then immediately flash-frozen in liquid nitrogen and stored at -80°C until RNA isolation and sequencing was performed.