Induction of diabetes in cynomolgus monkey with one shot of analytical grade streptozotocin

摘要

Backgrounds:Streptozotocin(STZ)-induced diabetic monkey is a wide used preclinical animal model for the investigation of diabetes such as islet transplantationand development of diabetic drugs.There are serious side effects of this method,including nausea,emesis,weight loss,liver damage,renal failure,and metabolic acidosis.In order to reduce the side effects,diabetic monkeys were induced using clinicalgrade STZ.However,clinical-grade STZ is not available in China.Here,we establised a method by using 100 mg/kg analytical-grade STZ to induce complete diabetes in cynomolgus monkey without generating adverse effects to liver and renal.Methods:Three cynomolgus monkeys were used in this study.100 mg/kg STZ dissolved in normal saline and infused through vein line in 5 minutes after indwelling catheter in the carotid artery and jugular vein.After the STZ administration,blood glucose levels were examined every 1 or 2 hours in the first 48 hours.Then,blood glucose levels were examined twice per day during the first week after the STZ injection.Insulin and C-peptide levels were measured by ELISA.Blood chemistry of hepatic and renal function tests were performed.Insulin and glucagon expression in the islet of diabetic monkey and normal monkey were examined by immunohistochemistry assays.Results:The stimulated C-peptide level(Intravenous glucose tolerance test)which is less than 0.5 ng/mL,the triphasic blood glucose response and the destroyed β cell suggested the complete induction of diabetes model.No apparent adverse effects were observed including no signs of vomiting and toxicity after STZ injection.Conclusion:In summary,we established a safe and reproducible STZ-induced diabetic cynomolgus monkey model for islet transplantation which will be used to develop novel approaches for the treatment of diabetes.