Alterations of Adenine Nucleotide Metabolism and Function of Blood Platelets in Patients With Diabetes

Abstract

Increased activity of blood platelets contributes to vascular complications in patients with diabetes. The aim of this work was to investigate whether persisting hyperglycemia in diabetic patients generates excessive accumulation of ATP/ADP, which may underlie platelet hyperactivity. Platelet ATP and ADP levels, thiobarbituric acid-reactive species synthesis, and aggregation of platelets from patients with diabetes were 18 -82% higher than in platelets from healthy participants. In patients with diabetes, platelet stimulation with thrombin caused about two times greater release of ATP and ADP than in the healthy group while decreasing intraplatelet nucleotide content to similar levels in both groups. This indicates that the increased content of adenylate nucleotides in the releasable pool in the platelets of diabetic patients does not affect their level in metabolic cytoplasmic/mitochondrial compartments. Significant correlations between platelet ATP levels and plasma fructosamine, as well as between platelet ATP/ADP and platelet activities, have been found in diabetic patients. In conclusion, chronic hyperglycemia-evoked elevations of ATP/ADP levels and release from blood platelets of patients with diabetes may be important factors underlying platelet hyperactivity in the course of the disease.

Metabolic and Hemostatic Parameters in Pre-Diabetes and Newly Diagnosed Type 2 Diabetes

“…Increased glucose influx into megacariocytes significantly contributes to the increased thrombin-evoked depletion of cyclic nucleotides, and also increased activity of enzymes involved in glycolytic, acetyl-CoA synthesis, and fatty acid-synthesizing pathways [22]. Insulin also stimulates cell cycle and the processes of megakaryocytic cell-line differentiation [23].…”

High glucose enhances CD39 expression in vascular endothelial cells

“…Consequently, CD39 has been proposed as a potential target for treatment of patients with complications caused by platelet activation [11][12][13]. CD39 is an ecto-enzyme expressed on VECs and is an important player in the regulation of inflammation and platelet activation, associated with DM complications [14,15]. However, it has not been reported if hyperglycemia has effects of CD39 in VECs.…”

Parameters of metabolism and hemostasis in patients with type 1 diabetes mellitus and microgiopathy of different severity

“…Избыточный приток глюкозы в мегакариоциты, а так же ее прямое и опосре-дованное (неферментативное гликозилирование, образование свободных радикалов и т.д.) воздействие на тромбоциты, меняет биохимию КП, повышая активность гликолитических фермен-тов, модифицируя метаболизм ионизированного кальция, мем-бранных фосфолипаз, синтез эйкозаноидов [7,8,9]. Конформационные изменения тромбоцитов с нарушением про-цессов агрегации, секреции, тромбоксансинтетической и эндоте-лий-поддерживающей функции расцениваются в качестве ключевых в развитии атеросклероза и тромбообразования [10].…”