Augmentation of streptozotocin-induced hyperglycemia in mice by prior treatment with complete Freund's adjuvant.
The effect of complete Freund's adjuvant (CFA), in combination with streptozotocin (STZ), on pancreatic insulin content, plasma glucose, and pancreatic histopathology were studied in male Balb/c mice. One injection of CFA, followed 24 h later by a single dose of 100 mg/kg of STZ (group I), produced a 92% (p less than 0.01) reduction in pancreatic insulin, a 54% (p less than 0.01) increase in glucagon content, and severe hyperglycemia. The depletion of pancreatic insulin was associated with degranulation, necrosis of beta cells, and reduction of the apparent islet size. Focal pancreatitis, without apparent islet inflammation, occurred in all animals in this group. After treatment with STZ alone (group II), pancreatic insulin content decreased 73% (p less than 0.01), whereas plasma glucose levels, even though being in the hyperglycemic range, were significantly lower (p less than 0.02) than the mice in group I. Although pyknotic and hypertrophic cell nuclei could be observed in several islets of mice from group II, major histopathological changes, such as pancreatitis and extensive beta cell necrosis seen in group I, were absent. The results show that in the Balb/c mouse strain, a nonspecific insult by CFA prior to a cell-specific cytotoxic insult markedly enhanced destruction of beta cells and the development of hyperglycemia.