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

Lee, Edmond S. ; Jiang, Jianjie ; Sund, Greg C. ; Simonson, William T. ; Graham, Jinko ; Dietsch, Greg ; Schimpf, Brian ; Bieg, Sabine ; Peterman, Gary and Lernmark, Åke LU orcid (1999) In Diabetes 48(1). p.43-49
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 =... (More)

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.

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author
; ; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
in
Diabetes
volume
48
issue
1
pages
43 - 49
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:9892221
  • scopus:0032910939
ISSN
0012-1797
DOI
10.2337/diabetes.48.1.43
language
English
LU publication?
no
id
2c10f0d9-8cd7-481a-832b-6d4ebc3ef9ba
date added to LUP
2019-06-30 23:33:05
date last changed
2024-03-13 08:17:44
@article{2c10f0d9-8cd7-481a-832b-6d4ebc3ef9ba,
  abstract     = {{<p>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.</p>}},
  author       = {{Lee, Edmond S. and Jiang, Jianjie and Sund, Greg C. and Simonson, William T. and Graham, Jinko and Dietsch, Greg and Schimpf, Brian and Bieg, Sabine and Peterman, Gary and Lernmark, Åke}},
  issn         = {{0012-1797}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  pages        = {{43--49}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{Recombinant human platelet-activating factor acetylhydrolase reduces the frequency of diabetes in the diabetes-prone BB rat}},
  url          = {{http://dx.doi.org/10.2337/diabetes.48.1.43}},
  doi          = {{10.2337/diabetes.48.1.43}},
  volume       = {{48}},
  year         = {{1999}},
}