Effect of insulin treatment in streptozocin-induced diabetic rats on in vitro platelet function and plasma von Willebrand factor activity and factor VIII-related antigen.
Diabetes mellitus is associated with altered platelet function and endothelial damage, but their relationship remains unclear. We examined the effect of short-term metabolic control with insulin in 14- and 28-day streptozocin-induced diabetic rats on alterations in in vitro platelet aggregation and serotonin release. Endothelial damage was assessed by plasma concentrations of von Willebrand factor activity (VIIIR:WF) and factor VIII-related antigen (VIIIR:Ag). Insulin was administered for 5 or 7 days at 9 or 21 days, respectively, after streptozocin. Enhanced platelet aggregation responses to adenosine diphosphate (ADP) and thrombin occurred after both durations of diabetes. Insulin therapy returned ADP-induced, but not thrombin-induced, responses to normal. Enhanced thrombin-induced platelet release of serotonin occurred at both times. Collagen-induced platelet release was enhanced in 28-day diabetic rats. Insulin therapy returned these responses to normal. Plasma concentrations of VIIIR:WF and VIIIR:Ag were elevated in 28-day, but only VIIIR:WF was elevated in 14-day diabetic rats. Insulin therapy reduced the elevated levels of VIIIR:Ag in 28-day diabetic rats, but had little effect on either parameter after the shorter duration of diabetes. In summary, Enhanced platelet aggregation and increased release of serotonin occur shortly after the induction of diabetes by streptozocin in adult rats. These platelet changes precede alterations of endothelial function, as determined by plasma VIIIR:WF and VIIIR:Ag levels. Platelet changes respond more rapidly to insulin therapy than do endothelial changes in diabetic rats. The duration of diabetes before insulin therapy does not affect these relationships.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000941:Antigens / Q000032:analysis*; D001779:Blood Coagulation Factors / Q000032:analysis*; D001792:Blood Platelets / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000188:drug therapy; D005169:Factor VIII / Q000032:analysis / Q000276:immunology*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D010974:Platelet Aggregation; D051381:Rats; D011919:Rats, Inbred Strains; D012310:Ristocetin / Q000494:pharmacology; D012701:Serotonin / Q000097:blood; D013917:Thrombin / Q000494:pharmacology; D014841:von Willebrand Factor / Q000032:analysis*
D000941:Antigens; D001779:Blood Coagulation Factors; D007328:Insulin; D014841:von Willebrand Factor; D012310:Ristocetin; D012701:Serotonin; D005169:Factor VIII; D013917:Thrombin