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⁺]₁ 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⁺]₁ 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.