Effects of ginkgolide B, a platelet-activating factor inhibitor on insulitis in the spontaneously diabetic BB rat

Autoimmunity. 1991;9(3):225-35. doi: 10.3109/08916939109007648.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Disease Models, Animal
  • Diterpenes*
  • Dose-Response Relationship, Drug
  • Eosinophils / immunology
  • Female
  • Ginkgolides
  • Immunohistochemistry
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / immunology
  • Islets of Langerhans / pathology
  • Lactones / pharmacology*
  • Male
  • Pancreatitis / drug therapy*
  • Pancreatitis / etiology
  • Pancreatitis / immunology
  • Platelet Activating Factor / antagonists & inhibitors*
  • Rats
  • Rats, Inbred BB

Substances

  • Diterpenes
  • Ginkgolides
  • Lactones
  • Platelet Activating Factor
  • ginkgolide B