Altered cellular signalling and decreased platelet sensitivity to adenosine in insulin-dependent diabetic patients with proliferative retinopathy

Platelets from patients with insulin-dependent diabetes with proliferative retinopathy showed the same reactivity to ADP as those from control subjects. Responsiveness of platelets to the aggregation inhibitor adenosine and to the analogue N-ethylcarboxamidoadenosine was decreased in diabetes. In contrast, responsiveness to the anti-aggregatory effects of prostaglandin I 2 was not significantly altered in diabetes. Platelets from diabetic patients exhibited decreased formation of cyclic AMP in response to N-ethylcarboxamidoadenosine compared with those from control subjects. In contrast, when adenylyl cyclase was stimulated by prostaglandin I 2 or by forskolin, no differences in cyclic AMP formation were observed between control and diabetic platelets. Diabetes was associated with an apparent loss of high-affinity binding of [ 3 H]N- ethylcarboxamidoadenosine platelet membranes. Possible mechanisms that could contribute to this diabetes-induced change in signalling through the platelet A 2 adenosine receptor are discussed.