Islet transplant model in nonhuman primates: use of streptozotocin

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease resulting from progressive destruction of the insulin-producing pancreatic β cells. Insulin-dependent diabetes mellitus is a common disease, the second most prevalent chronic illness in children. The clinical results reported by the Edmonton group in recipients of allogeneic islet grafts, who all achieved at least temporary insulin independence, have rekindled interest in islet transplantation as a therapy for IDDM. However, for islet transplantation to become the therapy of choice, it is essential to (1) overcome the shortage of donor tissue; (2) develop islet-friendly immunosuppressive protocols; (3) develop donor-specific tolerance; and (4) improve the rate of long-term engraftment as to rival outcomes with whole pancreas organ transplantation. As improvements are needed, a reliable diabetic animal model to develop strategies to improve clinical outcomes is important. The nonhuman primates are well suited for this purpose, although spontaneous diabetes in large animals is rare (J Clin Invest 1996;98:1417-22). Thus, induction of diabetes is necessary in this model. A nonhuman primate diabetic model using streptozotocin with stable insulin dependence has been achieved in several laboratories and will be discussed here.