Protection from BB rat diabetes by the platelet-activating factor inhibitor BN50730

Autoimmunity. 1993;16(4):259-66. doi: 10.3109/08916939309014644.

Abstract

The platelet-activating factor inhibitor BN50730, a hetrazepine, was injected intraperitoneally daily from 30 days of age into diabetes-prone BB rats. While 96% (22/23) Tween 80 injected control rats developed diabetes, 0.05 mg/kg BN50730 decreased the frequency to 72% (17/24; n.s.) and 0.5 mg/kg to 56% (14/25; p < 0.01). Mean onset age in controls was 81 +/- 9 days (mean +/- SD), but BN50730 delayed onset to 87 +/- 15 days in the low and 93 +/- 12. days (p < 0.01) in high dose rats. The relative degree of insulitis was reduced in both low (p < 0.01) and high (p < 0.05) dose treated groups. Serum insulin in young prediabetic controls decreased from 84 +/- 34 microU/ml to 38 +/- 20 in the 22 rats developing diabetes (p < 0.001). Serum insulin in BN50730-protected compared to unprotected rats was 114 +/- 49 and 32 +/- 22 (p < 0.001) in the low, and 91 +/- 46 and 21 +/- 15 (p < 0.001) microU/ml in the high dose group, respectively. Increased serum insulin correlated with preserved islet beta cells and decreased insulitis. Treatment did not affect thyroiditis. Thus, platelet-activating factor may be involved in insulitis pathogenesis and platelet-activating factor inhibitors may decrease autoimmune beta cell destruction.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / prevention & control*
  • Azepines / administration & dosage
  • Azepines / pharmacology
  • Azepines / therapeutic use*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Insulin / blood
  • Islets of Langerhans / pathology
  • Male
  • Platelet Activating Factor / antagonists & inhibitors*
  • Platelet Activating Factor / physiology
  • Rats
  • Rats, Inbred BB*
  • Tetrazoles / administration & dosage
  • Tetrazoles / pharmacology
  • Tetrazoles / therapeutic use*
  • Thienopyridines
  • Thyroid Gland / pathology
  • Thyroiditis, Autoimmune / blood
  • Thyroiditis, Autoimmune / genetics
  • Thyroiditis, Autoimmune / pathology
  • Triazoles*

Substances

  • Azepines
  • Insulin
  • Platelet Activating Factor
  • Tetrazoles
  • Thienopyridines
  • Triazoles
  • BN 50730