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 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 beta-cells were protected from insulitis by rPAF-AH.
Lee
E S
ES
Department of Medicine, University of Washington, Seattle 98195, USA.
Jiang
J
J
Sund
G C
GC
Simonson
W T
WT
Graham
J
J
Dietsch
G
G
Schimpf
B
B
Bieg
S
S
Peterman
G
G
Lernmark
A
A
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D003920:Diabetes Mellitus / Q000453:epidemiology* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D020022:Genetic Predisposition to Disease; D007150:Immunohistochemistry; D015994:Incidence; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000473:pathology / Q000517:prevention & control; D010741:Phospholipases A / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D011913:Rats, Inbred BB; D011994:Recombinant Proteins; D016019:Survival Analysis
D007328:Insulin; D011994:Recombinant Proteins; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase