Induction of diabetes in rhesus monkeys and establishment of insulin administration strategy.

ABSTRACT

OBJECTIVES: The diabetic rhesus monkey seems to be a useful model for preclinical investigations of islet transplantation and new drug treatments for type 1 diabetes mellitus (T1DM). Information is limited regarding a standard technique to induce and assess diabetes in rhesus monkeys as well as the strategy to apply insulin administration. Herein, we have established and characterized a model of diabetic rhesus macaques. METHODS: Four monkeys were divided into 2 groups of 2 each group 1, total pancreatectomy; and group 2, partial pancreatectomy (75%) with low-dose streptozotocin (STZ) administration. Pancreatic function was measured using intravenous glucose tolerance tests before the operation. Spiral computed tomography (CT) scans of the pancreas were obtained before and after pancreatectomy. Fasting blood glucose and postprandial blood glucose levels were monitored twice daily using blood samples from the fingers or toes. Various types and doses of insulin were administered twice daily. We performed regular assessments of hematological and serum biochemical parameters, insulin, and C-peptide. RESULTS: Both total pancreatectomy and partial pancreatectomy (75%) with STZ administration induced T1DM in rhesus monkeys; there was interindividual variation in the STZ dose. Excluding C-peptide and insulin, the hematological and serum biochemical parameters did not differ significantly from normal values postoperatively. The various insulin treatment strategies are achieved stable blood glucose (BG) levels. CONCLUSIONS: STZ injection after partial pancreatectomy may be a safe, reproducible method to induce T1DM. Porcine insulin administration was a safe, economical method to control BG levels in a diabetic rhesus monkey before islet transplantation.