Streptozotocin Induced Diabetes in Minipig: A Case Report of a Possible Model for Type 1 Diabetes?

Abstract

Studies on the pathogenic process in type 1 diabetes are often performed in animal models. Low-dose administration of streptozotocin has been used to induce diabetes with pathological alterations similar to human type 1 diabetes in the animals. Rodent models are frequently used but there is a need of developing new models including larger animals. In this study we wanted to investigate to what extent a minipig was sensitive to low-dose streptozotocin for induction of diabetes with features of human Type 1 diabetes. A female Göttingen minipig received two low-doses (40 mg/kg) of streptozotocin with an 11-day interval. Serum was analysed for the presence of the enzyme glutamic acid decarboxylase, isoform 65, (GAD65) and autoantibodies against glutamic acid decarboxylase, isoform 65 (GAD65A), isoform 67 (GAD67A), insulinoma antigen 2 (IA-2) and insulin (IAA). Pancreas tissue was fixated in formaldehyde and was sent for pathoanatomical examination. The minipig became hyperglycaemic after the second injection of streptozotocin. The pathoanatomical examination showed atrophy of the beta-cell population, depletion of insulin with preserved glucagon content. There was no sign of insulitis. Both GAD65 and GAD65A were detected while GAD67A and IAA were absent. It is concluded that chronic diabetes developed after low-dose streptozotocin injection in a female minipig with the characteristics of the end stage of type 1 diabetes. This pilot study suggests that minipigs show promise as a model to induce diabetes by injections of low-dose streptozotocin.