Figure 1.

Mechanisms of calcineurin-inhibitor induction of pancreatic beta cell toxicity in new onset diabetes mellitus after transplant.

Ca²⁺, calcium ions; NFATc, cytoplasmic nuclear factor of activated T cells

Calcineurin-inhibitor (CNI) causes new onset diabetes after transplant (NODAT) by producing pancreatic beta cells toxicity with reduction in insulin secretion and a cellular resistance to the effect of insulin. It causes hypomagnesemia which impairs beta cell insulin secretion by increasing cytosolic calcium ion concentration. CNI prevents dephosphorylation of NFATc, a transcription factor for genes that promotes islet cell proliferation. It also reduces efficient insulin secretion by causing functional alteration of glucokinase enzyme. Finally, a high dose of CNI causes apoptosis of pancreatic beta cells.