Protection from BB rat diabetes by the platelet-activating factor inhibitor BN50730.
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.
University of Washington, School of Medicine, Seattle 98195.
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D000367:Age Factors; D000818:Animals; D001327:Autoimmune Diseases / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D011913:Rats, Inbred BB; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D058924:Thienopyridines; D013961:Thyroid Gland / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000097:blood / Q000235:genetics / Q000473:pathology; D014230:Triazoles
D001381:Azepines; D007328:Insulin; D010972:Platelet Activating Factor; D013777:Tetrazoles; D058924:Thienopyridines; D014230:Triazoles; C066686:BN 50730