Figure 1. Immunosuppressants inhibit β cell recovery after targeted ablation.

(A) Normal β cell mass and glucose homeostasis in transgenic mice before application of doxycycline, the inducer of β cell death, in the transgenic animal model used by Nir et al. in this issue of the JCI (5). DTA, diphtheria toxin A. (B) Doxycycline treatment activates the expression of diphtheria toxin A specifically in the β cells of the pancreas, reducing β cell mass by 80% and causing hyperglycemia. (C) Regeneration of β cell mass through β cell proliferation and normalization of glucose homeostasis after doxycycline withdrawal. In the presence of Sirolimus and Tacrolimus, the immunosuppressants used in human islet transplantation, the regenerative response of the β cells is inhibited, and hyperglycemia persists.