Prostaglandins and Medicine 7: 341- 347, 1981 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQP REFRACTORINESS OF DIABETIC PLATELETS TO INHIBITORY PROSTAGLANDINS M. Lagarde, P. Berciaud, M. Burtin & M. Dechavanne INSERM U63, Institut Pasteur, Laboratoire d'Hemobiologie Faculte Alexis Carrel 69372 Lyon Cedex 2, France (reprint requests to ML) ABSTRACT Inhibition of collagen-induced platelet aggregation by either endothe- lial extracts, prostacyclin, prostaglandin El or prostaglandin D2 was investigated. The inhibition was less efficient with diabetic plate- lets than with platelets from normal donors. The refractoriness of diabetic platelets to inhibitory prostaglandins was observed both with platelet-rich plasma and platelets isolated from their plasma. Moreover, levels of cyclic AMP in resting platelets and after stimulation by either PGEl or PGD2 were lower in diabetic platelets than in normal platelets. It is concluded that the weaker response of diabetic plate- lets to inhibitory prostaglandins could be related to their content in cyclic AMP. INTRODUCTION Platelets in patients with diabetes mellitus have been shown to be hy- persensitive to aggregating agents by several groups (See the review of Bern, I). One of these groups has recently reported an increased pro- duction of a prostaglandin E-like material in diabetic-rich plasma (2) and a refractoriness of diabetic platelets to imidazole (3), a thrombo- sane synthetase inhibitor (4). Another group has reported an increase of thromboxane B2 formation by diabetic platelet-rich plasma (5). In a recent paper, using diabetic platelets isolated from their plasma, we described a normal synthesis of thromboxane BP from exogenous arachi- donic acid but an increased synthesis under thrombin stimulation (6). In the same paper, we also described an increase of the half-life of thromboxane A2 in diabetic plasma. In this study, we investigated the response of collagen-induced aggre- gation to endothelial cell extract and to PGI2, PGE1, PGD2, all pros- 341