Abstract

Common marmosets have attracted considerable attention as a small standard primate model in biomedical research. However, no marmoset diabetes model is available. Here, we established a marmoset diabetes model via the combination of partial pancreatectomy and intravenous streptozotocin (STZ). A partial pancreatectomy was performed in 11 common marmosets and multiple STZ doses were intravenously administered. Diabetes was diagnosed upon sustained hyperglycaemia (nonfasting blood glucose level >200 mg/dl). Blood glucose and biochemistry were periodically assessed, in addition to glucose tolerance testing, continual blood glucose determination using a continuous glucose monitoring system, urine testing and histological evaluation. In 8 of the 11 animals (73%), diabetes mellitus was induced. The diabetic marmosets also showed abnormal intravenous and oral glucose tolerance test results. Blood glucose levels decreased in response to human insulin administration. The hyperglycaemic state was irreversible and persisted for more than 3 months, and the animals’ condition was manageable via daily insulin administration. Thus, diabetes can be successfully induced and maintained in the common marmoset via partial pancreatectomy and STZ administration. This protocol effectively generates a valuable animal model for studying disease pathogenesis, risk factors and therapeutic interventions, including islet transplantation.

Highlights

  • Type 1 diabetes mellitus, characterised by progressive destruction of insulin-producing cells, is an organ-specific autoimmune disease

  • In this study, we investigated whether the combination of partial pancreatectomy and STZ administration could successfully and safely induce diabetes mellitus type 1 in the common marmoset and physiologically and histologically assessed the model

  • Body weight was often reduced by the pancreatectomy, STZ administration and diabetic conditions (Supplemental Fig. S2)

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Summary

Introduction

Type 1 diabetes mellitus, characterised by progressive destruction of insulin-producing cells, is an organ-specific autoimmune disease. A promising alternative due to its potentially unlimited supply involves transplantation of pancreatic islet-like cells produced from embryonic stem cells and somatic stem cells[4,5]. These cell therapies are highly encouraging approaches, the preclinical effectiveness and safety data need to justify the initiation of any clinical trials. Pancreatectomy or streptozotocin (STZ) can be used to induce a diabetes mellitus type 1 model in many animal species[11,12]. In this study, we investigated whether the combination of partial pancreatectomy and STZ administration could successfully and safely induce diabetes mellitus type 1 in the common marmoset and physiologically and histologically assessed the model

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