Immune insulitis and antibodies to nucleic acids induced with streptozotocin in mice

Streptozotocin (STZ), a known beta cell toxin, given in a single injection of either a high (100 mg/kg body weight) or a low dose (60 mg/kg body weight) to young (45 days old) CD-I mice induced permanent hyperglycaemia which led to insulin-dependent diabetes (IDD). Further study, however, revealed that the course of the disease was strikingly different between the groups. The average latent period of the high-dose group (n = 20) before the development of hyperglycaemia was only 3 days while that of the low-dose group was 7 weeks (n = 30). Islets of pancreas in the high-dose group showed extensive acute necrosis of the islets with only two out of 20 showing limited mononuclear cell infiltration. In contrast, 20 out of 30 mice in the low-dose group had 45% of their islets heavily infiltrated with mononuclear cells (P less than 0.001). In addition, the deposition of IgG was found in 40% of the islets in 23 out of 30 mice in the low-dose group, in contrast to only two out of 20 in the high-dose group (P less than 0.005). The incidence of antibody to nucleic acids, polyadenylic-polyuridylic acid, polyinosinic-polycytidylic acid, single-stranded DNA and anti-nuclear antibody was significantly higher in the low-dose group as compared to the high-dose group or controls (P less than 0.01). Since the findings in the low-dose group are similar to pathological and serological changes reported in man with recent-onset IDD, this model should be of value in the study of the pathogenesis of this disease.