Simultaneous Subtotal Pancreatectomy and Streptozotocin Injection for Diabetes Modeling in Cynomolgus Monkeys.

BACKGROUND: In an experimental animal model of islet transplantation, stable induction of insulin-dependent diabetes mellitus (IDDM) and islet isolation from donor pancreas are essential. Total pancreatectomy for IDDM induction and islet procurement in nonhuman primates leads to unwanted loss of exocrine function and may lead to morbidities associated with IDDM.

METHODS: IDDM induction with streptozotocin (STZ) is associated with drug toxicity of STZ and necessitates the killing of another animal for islet procurement. In this study, we performed a subtotal pancreatectomy combined with reduced STZ injection to induce IDDM and procure islets in a nonhuman primate model.

RESULTS: Twelve cynomolgus monkeys received low-dose STZ injections (60 mg/kg) simultaneously with subtotal pancreatectomy. All monkeys recovered from the procedure without complications. IDDM was induced in the animals. 57,691 ± 16,050 islets were isolated from the resected pancreas and transplanted into other monkeys.

CONCLUSIONS: Simultaneous subtotal pancreatectomy and low-dose STZ injection represent an effective and safe method to create an animal model of insulin dependence diabetes, while at the same time providing sufficient amounts of fresh islet cells for allotransplantation without requiring killing of additional animals.