Altered cellular Ca2+ and Na+ transport in diabetes mellitus

Platelet intracellular Ca2+ concentration ([Ca2+]i) and its response to stimuli (ADP and thrombin) were studied in 15 insulin-dependent and 22 non-insulin-dependent diabetes mellitus patients with the fluorescent probe Fura 2. The activity of Ca2(+)-ATPase and Na(+)-K(+)-ATPase, membrane fluidity, and cholesterol and phospholipid content were also determined in platelet membranes. Compared with control subjects, diabetic patients showed 1) increased platelet [Ca2+]i in the resting state, 2) higher Ca2+ levels after stimulation with thrombin and ADP, due entirely to increased resting concentrations, 3) reduced activity of Na(+)-K(+)-ATPase, 4) increased activity of Ca2(+)-ATPase, 5) higher fluidity of the platelet membrane, and 6) increased membrane concentration of total phospholipids. Na(+)-K(+)-ATPase activity was inversely related to platelet [Ca2+]i in each group studied, whereas Ca2(+)-ATPase activity was positively correlated with intracellular Ca2+ levels. The data obtained in diabetic subjects suggest an abnormality in Ca2+ and Na+ transport across the platelet membrane that might be responsible for the reported platelet hyperreactivity to stimuli in diabetes.