Proposed metabolic dysfunctions in diabetic microthromboses and microangiopathy.
This report describes, at least in part, the role of prostaglandin and cyclic nucleotide metabolism in the etiology of the vascular disease associated with diabetes mellitus. Alterations in this metabolism seem associated with induction of platelet aggregation leads to microthromboses leads to microangiopathy sequences that are subtle but inexorable over a long period of time. Prostaglandins are generally elevated in blood from patients having frank signs of diabetic retinopathy when compared with nondiabetic subjects. Prostaglandin concentration remained elevated in diabetic retinopathy patients receiving indomethacin. We formed, therefore, the working hypothesis--yet to be fully tested either in patients or animal models with and without indomethacin treatment--that the increased prostacyclin (synthesized by endothelial microsomes) and cyclic-AMP production, both of which favor prevention of platelet aggregation, accompany the increased concentration of one or more of the prostaglandin E and F compounds. Concurrently, there may be an accompanying reduction of thromboxane A2 (synthesized by platelet microsomes) and cyclic-GMP (both of which favor platelet aggregation) production in the diabetic patients. The elevated prostaglandin in the diabetic patients not receiving indomethacin could possibly be directed toward slowing but not preventing the progression of the complex disease process in diabetes.
D000527:Alprostadil; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D003094:Collagen / Q000097:blood; D000242:Cyclic AMP / Q000097:blood*; D006152:Cyclic GMP / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D003925:Diabetic Angiopathies / Q000209:etiology*; D015237:Dinoprost; D015232:Dinoprostone; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008954:Models, Biological; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000097:blood*; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D013928:Thromboxane A2 / Q000494:pharmacology
D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D000001:Calcimycin; D013928:Thromboxane A2; D003094:Collagen; D015237:Dinoprost; D000242:Cyclic AMP; D000527:Alprostadil; D006152:Cyclic GMP; D015232:Dinoprostone; D001241:Aspirin; C100006:prostaglandin F1; D007213:Indomethacin