No Time to Die—How Islets Meet Their Demise in Transplantation

Islet transplantation represents an effective treatment for patients with type 1 diabetes mellitus (T1DM) and severe hypoglycaemia unawareness, capable of circumventing impaired counterregulatory pathways that no longer provide protection against low blood glucose levels. The additional beneficial effect of normalizing metabolic glycaemic control is the minimisation of further complications related to T1DM and insulin administration. However, patients require allogeneic islets from up to three donors, and the long-term insulin independence is inferior to that achieved with solid organ (whole pancreas) transplantation. This is likely due to the fragility of islets caused by the isolation process, innate immune responses following portal infusion, auto- and allo-immune-mediated destruction and β-cell exhaustion following transplantation. This review covers the specific challenges related to islet vulnerability and dysfunction that affect long-term cell survival following transplantation.