Inhibition of heparin-catalyzed human antithrombin III activity by nonenzymatic glycosylation. Possible role in fibrin deposition in diabetes.

Abstract:

:The effect of nonenzymatic glycosylation on the biologic function of human antithrombin III was evaluated using a chromogenic thrombin substrate assay in the presence of catalytic amounts of heparin. Experimental conditions that increased the rate of nonenzymatic protein glycosylation were associated with decreases in the thrombin-inhibiting activity of antithrombin III. This glycosylation-induced inhibition of heparin-catalyzed antithrombin III activity was completely reversible by preassay incubation with excess sodium heparin. These observations provide a biochemical explanation for the heparin-reversible, accelerated fibrinogen disappearance rate induced by hyperglycemia in diabetic patients. Defective inhibition of the coagulation cascade induced by excessive nonenzymatic glycosylation of antithrombin III in vivo could contribute to accumulation of fibrin in various diabetic tissues.

journal_name

Diabetes

journal_title

Diabetes

authors

Brownlee M,Vlassara H,Cerami A

doi

10.2337/diab.33.6.532

subject

Has Abstract

pub_date

1984-06-01 00:00:00

pages

532-5

issue

6

eissn

0012-1797

issn

1939-327X

journal_volume

33

pub_type

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