Recombinant human platelet-activating factor acetylhydrolase reduces the frequency of diabetes in the diabetes-prone BB rat

Platelet-activating factor (PAF) has been implicated in the development of type 1 diabetes, Our previous studies have suggested that PAF inhibitors re duce insulitis and the frequency of diabetes in BB rats, In this study seru m PAF levels were reduced to address the hypothesis that PAF is important f or the development of insulitis. From the age of 35 days on, DP-BB rats wer e treated with human recombinant PAF acetylhydrolase (rPAF-AH), which effic iently inactivates PAF Our data indicate that intraperitoneal injections of rPAF-AH reduce the incidence of diabetes in the DP-RR rat. Daily intraperi toneal injections of 6.0 mg/kg body wt rPAF-AH reduced the frequency of dia betes in saline-injected rats from 90%; (27/30) to 57% (17/30) (P = 0.004). As found by morphometric analysis on pancreatic islets, DP-BB rats protect ed from diabetes had less severe degrees of insulitis in a dose-dependent m anner. DP-BB rats protected by rPAF-AH also had a higher percentage of insu lin-positive cells in pancreas sections compared with those from diabetic a nimals, We therefore speculated that the beta-cells were protected from ins ulitis by rPAF-AH.