Effects of ginkgolide B, a platelet-activating factor inhibitor on insulitis in the spontaneously diabetic BB rat.
The BB rat spontaneously develops insulin-dependent diabetes mellitus (IDDM) in association with marked insulitis in the islet of Langerhans. Since platelet-activating factor (PAF-acether) is involved in allergic and inflammatory reactions, we tested a PAF antagonist, Ginkgolide B (BN 52021) for potential effects on islet inflammation and diabetes. Diabetes prone BB/Wor rats were treated daily from weaning at 25 days until 105 days of age with either saline (n = 30, controls), 10 (n = 25, low dose) or 20 (n = 30, high dose) mg/kg body weight of BN 52021. The overall incidence of IDDM was unaffected by treatment. Quantitative analysis of insulin area showed a dose-dependent protection of beta cells by Ginkgolide B, reflected in a 6- (low dose) to 8-fold (high dose) (P less than 0.01-0.005) increase in the insulin/glucagon cell ratio compared to the saline treated rats. Ginkgolide B reduced severe insulitis from 84% in the saline rats developing IDDM to 59% (n.s.) in the low and to 33% (P less than 0.001) in the high dose group. These data suggest that PAF inhibitors may prove useful in immunomodulator therapy of IDDM since beta cells are preserved.
Beck
J C
JC
Department of Medicine, University of Washington, Seattle 98195.
Goodner
C J
CJ
Wilson
C
C
Wilson
D
D
Glidden
D
D
Baskin
D G
DG
Lernmark
A
A
Braquet
P
P
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000276:immunology; D005260:Female; D046934:Ginkgolides; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D010195:Pancreatitis / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D011913:Rats, Inbred BB
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; C045856:ginkgolide B