Poly I:C accelerates development of diabetes mellitus in diabetes-prone BB rat.

ABSTRACT

We developed a new experimental model of accelerated diabetes mellitus in the genetically susceptible diabetes-prone BB rat with the administration of the IFN-alpha inducer poly IC. With this model, there was both an increased incidence and accelerated onset of insulin-dependent-diabetes in poly IC-treated animals compared with saline-treated controls. All twelve rats administered poly IC (5 micrograms/gm body weight 3 times/wk) developed diabetes by 57 days of age (100%) compared with 1 of 27 (3.7%) saline-treated controls. Furthermore, the development of diabetes was accelerated in the poly IC-treated group (mean age +/- SE at onset 52.8 +/- 0.58 days) compared with saline-treated controls (89.3 +/- 2.4 days, P less than 0.01). Additionally, poly IC-treated rats had higher mean serum IFN-alpha levels than saline-treated rats at weeks 2 and 3 of treatment (210 vs. 27 and 183 vs. 25 U/ml, respectively, P less than 0.001). Poly IC treatment of 5 Wistar rats, the parental strain, which is not susceptible to diabetes, did not result in insulitis, diabetes, or hyperglycemia. The histopathologic findings of insulitis and decreased immunoreactive islet insulin in poly IC-accelerated diabetic BB rats and in BB rats with spontaneous diabetes suggest a similar pathophysiology.