Hypersensitivity to ADP of platelets from diabetic rats associated with enhanced fibrinogen binding.
Platelets from diabetic humans and animals are hypersensitive to ADP. The hypersensitivity to ADP of platelets from diabetic rats occurs independently of activation of the arachidonate pathway or release of dense granule contents. During platelet aggregation by ADP, fibrinogen binds to its receptor on platelets. We examined if the hypersensitivity to ADP of platelets from diabetic rats is associated with enhanced early binding of fibrinogen to its receptor on these platelets. Fibrinogen association with platelets from rats with spontaneous or streptozotocin-induced diabetes was significantly greater 10 s or 1 min after addition of ADP (10 microM) than with platelets from their corresponding control rats. Since enhanced fibrinogen association occurred with platelets from insulin-treated rats with spontaneous diabetes, and from rats with streptozotocin-induced diabetes that did not receive insulin, the enhanced fibrinogen binding is likely due to the diabetic state rather than to the administration of insulin or the mechanism responsible for the diabetes. Therefore, enhanced early fibrinogen association with platelets from diabetic rats is associated with their hypersensitivity to ADP.
Winocour
P D
PD
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Perry
D W
DW
Kinlough-Rathbone
R L
RL
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000209:etiology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D004351:Drug Resistance; D005340:Fibrinogen / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D051381:Rats; D011913:Rats, Inbred BB
D010980:Platelet Membrane Glycoproteins; D000244:Adenosine Diphosphate; D005340:Fibrinogen