Oxygen free radicals have been shown to interfere with pancreatic islet beta cell function and integrity, and have been implicated in autoimmune type 1 diabetes. We hypothesized that the spontaneous autoimmune type 1 diabetes of the BB rat would be prevented by in vivo administration of a free-radical spin trap, α-phenyl-N-tert-butylnitrone (PBN). Twenty-eight diabetes-prone (BBdp) and 13 non-diabetes-prone (BBn) rats received PBN (10 mg/kg) subcutaneously twice daily, and 27 BBdp and 12 BBn rats received saline as controls. Rats were treated from age 47 ± 6 days until diabetes onset or age 118 ± 7 days. PBN caused no growth, biochemical, or hematological side effects. Sixteen control BBdp rats became diabetic (BBd, mean age 77 ± 6 days) and six demonstrated impaired glucose tolerance (IGT rats). The incidence of diabetes and IGT was not different in PBN-treated BBdp rats. Saline-treated rats showed no differences in pancreatic malondialdehyde (MDA) contents of BBd, IGT rats, and the BBdp that did not develop diabetes, versus BBn rats (2.38 ± 0.35 nmoL/g). Among rats receiving PBN, BBn had lower pancreatic MDA than BBd and IGT rats (1.38 ± 0.15 vs. 1.88 ± 0.15 and 2.02 ± 0.24 nmoL/g, p < 0.05), but not than BBdp rats (1.78 ± 0.12 nmoL/g, ns). BBn rats receiving PBN also had lower pancreatic MDA than the saline controls (p < 0.05). Thus, PBN is remarkably nontoxic and is able to decrease MDA in the absence of the autoimmune process, but does not prevent diabetes. A combination of PBN with other complementary antioxidant agents may hold better promise for disease prevention.Key words: α-phenyl-N-tert-butylnitrone, type 1 diabetes mellitus, BB rats, lipid peroxidation, malondialdehyde, spin traps.
Type 1 Diabetes in the BB Rat: A Polygenic Disease