title: Effects of ginkgolide B, a platelet-activating factor inhibitor on insulitis in the spontaneously diabetic BB rat.
abstract: 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.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98195.
authors.forename: J C
authors.initials: JC
authors.lastname: Beck
authors.forename: C J
authors.initials: CJ
authors.lastname: Goodner
authors.forename: C
authors.initials: C
authors.lastname: Wilson
authors.forename: D
authors.initials: D
authors.lastname: Wilson
authors.forename: D
authors.initials: D
authors.lastname: Glidden
authors.forename: D G
authors.initials: DG
authors.lastname: Baskin
authors.forename: A
authors.initials: A
authors.lastname: Lernmark
authors.forename: P
authors.initials: P
authors.lastname: Braquet
mesh_terms: 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
chemical_list: D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; C045856:ginkgolide B