Background:Diabetic nonhuman primates (NHPs) are considered as the good models for both diabetes mellitus research and islet transplantation research safely into clinical applications. However, there are persistent hurdles to the advancement and large-scale application of these models in islet transplantation.

Common marmosets as a small standard primate model, has been attracting much attention in the research field of biomedical science. However, the marmoset diabetes model is not established yet. Here, we demonstrate marmoset diabetes model establishment by the combination of streptozotocine intravenous administration and partial pancreatectomy.

Methods: Ten animals were used. After evaluation of glucose metabolism, partial pancreatectomy was performed and streptozotocin (STZ) 100mg/kg to 200mg/kg of body weight were given multiple intravenously. Diagnosis of diabetes was made when sustained hyperglycemia (blood glucose level > 250 mg/dl) Blood glucose determination and a blood biochemistry inspection were conducted periodically, and we also implemented glucose insulin tolerance test and continual blood glucose determination by the continuous glucose monitoring (CGM) wearing, urine test and histological evaluation.

Results: The normal marmosets showed the similar blood glucose level and glucose tolerance reactivity with human. The marmoset islet showed the same size as the human islet histologically, and distribution of alpha cell and the beta cell inside the islet was also similar to the human islet. We established a safe and consistent induction of diabetes mellitus in common marmosets with a combination of partial pancreatectomy and a multiple administration of STZ. The non-fasting blood glucose levels were elevated from <200 mg/dl in pre-treatment stage to above 250 mg/dl in diabetic marmosets. Insulin dependent diabetic marmosets also had abnormal responses to intravenous and oral glucose tolerance tests. The blood glucose levels decreased in response to human insulin administration. The hyperglycemia state continued a few months and was irreversible.

Conclusions: We successfully induced and maintained diabetes in the common marmosets by partial pancreatectomy and STZ injection. This protocol is an effective method with which to generate valuable animal models for the research of disease pathogenesis, risk factors and therapeutic interventions including islet transplantation.

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