Abnormality in prostacyclin-stimulatory activity in sera from diabetics.
A reduction in prostacyclin (PGI2) production by vascular wall may cause platelet hyperaggregability in diabetics, which is considered to be a possible pathogenesis of diabetic vascular complications. In the present study, the presence of PGI2-stimulatory activity (PSA) in rat and human plasma-derived serum (PDS) was confirmed by cultured bovine aortic endothelial cells. PSA in PDS was significantly decreased in streptozotocin-induced diabetic rats and in patients with non-insulin-dependent diabetes mellitus (NIDDM). PDS from patients with NIDDM showed less PSA prior to the clinical onset of diabetic vascular complications, such as retinopathy and proteinuria. The reduction in PSA was still observed in dialyzed PDS from the patients with NIDDM. The nondialyzable PSA was heat-stable at 56 degrees C for 30 minutes and partially stable at 100 degrees C for five minutes. This activity was not extractable with diethylether and was precipitable with trichloroacetic acid. The study of Sephadex G-50 column chromatography showed that a major part of PSA in dialyzed PDS was found in the area of the molecular weight of 12,000 to 17,000 daltons. In conclusion, the reduction in PSA from diabetics may cause a reduction of PGI2 production by vascular wall, subsequently contributing to the development of diabetic vascular complications.
Inoguchi
T
T
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Umeda
F
F
Ono
H
H
Kunisaki
M
M
Watanabe
J
J
Nawata
H
H
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000328:Adult; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002478:Cells, Cultured; D002850:Chromatography, Gel; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003956:Dialysis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis / Q000097:blood*; D006801:Humans; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D001241:Aspirin