Platelets from diabetic subjects show diminished sensitivity to prostacyclin

Abstract

Prostacyclin, an unstable metabolite of arachidonic acid metabolism, has been shown to have potent platelet antiaggregatory and vasodilator activity. Available evidence suggests that arterial prostacyclin production is diminished in the diabetic state. In this study we have examined the sensitivity of platelets from diabetic subjects to the antiaggregatory effects of prostacyclin in vitro and report that platelets from some diabetic patients show diminished sensitivity to the antiaggregatory effects of prostacyclin. Thus diabetic subjects may not only have diminished prostacyclin production but also their platelets may be less sensitive to its effects. These findings may help to explain the increase in vascular disease observed in diabetic patients.

Diabetes and Antiplatelet Therapy in Acute Coronary Syndrome

“…73 In addition, platelets of DM patients have diminished sensitivity to the actions of NO and prostacyclin. 43,44 Endothelial dysfunction is another characteristic feature in DM patients that may result in a prothrombotic state through an increased production of tissue factor. 74 An upregulation of platelet ADP P2Y 12 receptor signaling, which suppresses cAMP levels, and a lower responsiveness to insulin have been suggested in patients with type 2 DM, leading to increased adhesion, aggregation, and procoagulant activity.…”

“…41,42 IRSindependent pathways are also involved in platelet hyperreactivity caused by insulin resistance such as impairment in platelet sensitivity to nitric oxide (NO) and prostacyclin. 43,44 Both mediators are released by the endothelium and retard platelet activation. Therefore, impaired response to NO and prostacyclin is associated with enhanced platelet reactivity.…”

“…41,42 Az IRS-től független folyamatok is hozzájárulnak az inzulinrezisztencia által kiváltott thrombocyta-hiperreaktivitáshoz, úgy mint a vérlemezkék nitrogén-monoxid (NO) és a prosztaciklin iránti csökkent érzékenysége. 43,44 Mindkét jelátvivő anyag az endotheliumból szabadul fel, és késlelteti a thrombocytaaktivációt. Így a nitrogén-monoxidra és prosztaciklinre adott káro-sodott válasz fokozott thrombocytareaktivitással jár.…”

Antiplatelet Therapy in Patients With Diabetes Mellitus and Acute Coronary Syndrome

“…5, 6 Several mechanisms are involved in this platelet dysfunction ( Figure 1): hyperglycemia enhances platelet aggregation by inducing P-selectin expression, 7 by activating protein kinase C (a mediator of platelet activation) 8 and by glycating platelet surface proteins, with consequent decrease in membrane fluidity and amplification of platelet adhesion. 9 Moreover, insulin resistance and/or deficiency in diabetic patients have been associated with impairment in the response to antithrombotic molecules (such as prostacyclin) 10 and contribute to platelet dysfunction by insulin receptor substrate-dependent effects, causing a rise in the intracellular calcium concentration and subsequent enhanced platelet degranulation. 11 Upregulation of glycoprotein (GP) IIb/IIIa surface receptors, 12 amplification of P2Y12 signaling, 13 and overproduction of reactive oxygen species 14 also contribute to the platelet dysfunction of diabetic patients; finally, metabolic conditions frequently associated with DM (ie, obesity, dyslipidemia and systemic inflammation) may also play a role.…”

Adrenoceptor-linked [45Ca2+] uptake in platelets from diabetic rats: a model for human platelets

“…For example J there are increases in alphaadrenoceptor but diminished beta-adrenoceptor activity in cardiac, smooth muscle and neural tissue (Tomlinson et al 1992). Furthermore J Betteridge et al (1982) have demonstrated that PGIrstimulated adenylate cyclase is significantly diminished in platelets from diabetic patients. Since beta-adrenoceptors are thought to act via activation of adenylate cyclase (Jakobs et ai.…”