TY - JOUR AU - Fathi, Ibrahim AU - Imura, Takehiro AU - Imura, Kozue AU - Goto, Megumi AU - Igarashi, Yasuhiro AU - Inagaki, Akiko AU - Kikkawa, Makiko AU - Ono, Fumiko AU - Iwata, Hiroo AU - Yasunami, Yohichi AU - Goto, Masafumi PY - 2019 DA - 2019/07/09 TI - A Simple and Effective Non-Human Primate Diabetic Model Combining Sub-Total Pancreatectomy and Low-Dose Streptozotocin Injection JO - OBM Transplantation SP - 071 VL - 03 IS - 03 AB - BACKGROUND. Current non-human primate diabetic models, namely those induced by total pancreatectomy or streptozotocin (STZ) injection, suffer from several disadvantages, including a long surgical procedure, the need for continual digestive enzyme replacement, and a delayed oral intake after total pancreatectomy and severe hypoglycemia and hepatic/renal toxicity with high-dose STZ injection. AIM. To construct and optimize a non-human primate diabetic model that avoids the disadvantages of current approaches and compare it to the STZ model. METHODS. Diabetes was induced in male Cynomolgus monkeys (n=4) by performing subtotal pancreatectomy followed by low-dose STZ injection (30 [n=1], 45 [n=2] and 60 [n=1] mg/kg). This model was compared to STZ injection only (60 [n=1] and 100 [n=9] mg/kg) regarding the development of diabetes (serum C-peptide and pancreatic anti-insulin staining), the liver (glutamine-ornithine-transaminase and glutamine-pyruvate-trasnaminase levels) and kidney functions (BUN and creatinine levels), and the general condition (weight loss, food intake, and activity). RESULTS. The serum C-peptide levels after glucose challenge in the combined model were comparable (0 ng/mL) to those with high-dose STZ injection (100 mg/kg). The absence of pancreatic insulin staining was demonstrated when 60 mg/kg STZ was used after subtotal pancreatectomy and with 100 mg/kg STZ injection only. The combined model did not suffer from hypoglycemic episodes and showed better activity and oral intake than the STZ-only model. Liver enzyme levels were markedly lower in the new model, while BUN and creatinine levels were higher than with STZ alone. CONCLUSIONS. Diabetes was successfully induced using the combined technique without the need for a lengthy operation or continual digestive enzyme replacement. In addition, the reduction in the pancreatic volume allowed for lower STZ utilization which led to less hepatic toxicity and the absence of hypoglycemic episodes. However, adequate fluid administration may be required to guard against renal STZ toxicity. SN - 2577-5820 UR - https://doi.org/10.21926/obm.transplant.1903071 DO - 10.21926/obm.transplant.1903071 ID - Fathi2019 ER -