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

Research output: Contribution to journalArticle

Abstract

Platelet-activating factor (PAF) has been implicated in the development of type 1 diabetes. Our previous studies have suggested that PAF inhibitors reduce insulitis and the frequency of diabetes in BB rats. In this study, serum PAF levels were reduced to address the hypothesis that PAF is important for the development of insulitis. From the age of 35 days on, DP-BB rats were treated with human recombinant PAF acetylhydrolase (rPAF-AH), which efficiently inactivates PAF. Our data indicate that intraperitoneal injections of rPAF-AH reduce the incidence of diabetes in the DP-BB rat. Daily intraperitoneal injections of 6.0 mg/kg body wt rPAF-AH reduced the frequency of diabetes 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 protected from diabetes had less severe degrees of insulitis in a dose- dependent manner. DP-BB rats protected by rPAF-AH also had a higher percentage of insulin-positive cells in pancreas sections compared with those from diabetic animals. We therefore speculated that the β-cells were protected from insulitis by rPAF-AH.

Details

Authors
  • Edmond S. Lee
  • Jianjie Jiang
  • Greg C. Sund
  • William T. Simonson
  • Jinko Graham
  • Greg Dietsch
  • Brian Schimpf
  • Sabine Bieg
  • Gary Peterman
  • Åke Lernmark
External organisations
  • University of Washington
  • Lilly Research Laboratories
Original languageEnglish
Pages (from-to)43-49
JournalDiabetes
Volume48
Issue number1
Publication statusPublished - 1999 Jan 1
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes