The platelet-activating factor inhibitor BN50730, a hetrazepine, was i
njected intraperitoneally daily from 30 days of age into diabetes-pron
e BB rats. While 96% (22/23) Tween 80 injected control rats developed
diabetes, 0.05 mg/kg BN50730 decreased the frequency to 72% (17/24; n.
s.) and 0.5 mg/kg to 56% (14/25; p < 0.01). Mean onset age in controls
was 81 +/- 9 days (mean +/-SD), but BN50730 delayed onset to 87 +/- 1
5 days in the low and 93 +/- 12. days (p < 0.01) in high dose rats. Th
e relative degree of insulitis was reduced in both low (p < 0.01) and
high (p < 0.05) dose treated groups. Serum insulin in young prediabeti
c controls decreased from 84 +/- 34 mu U/ml to 38 +/- 20 in the 22 rat
s developing diabetes (p < 0.001). Serum insulin in BN50730-protected
compared to unprotected rats was 114 +/- 49 and 32 +/- 22 (p < 0.001)
in the low, and 91+/-46 and 21 +/- 15 (p < 0.001) mu U/ml in the high
dose group, respectively. Increased serum insulin correlated with pres
erved islet beta cells and decreased insulitis. Treatment did not affe
ct thyroiditis. Thus, platelet-activating factor may be involved in in
sulitis pathogenesis and platelet-activating factor inhibitors may dec
rease autoimmune beta cell destruction.