Differential alterations of spontaneous and stimulated ⁴⁵Ca²⁺ uptake by platelets from patients with type I and type II diabetes mellitus

Diabetes mellitus (DM) is associated with hyperaggregability of platelets. Although the mechanisms underlying this abnormality remain unknown, Ca²⁺ imbalance has been implicated. Both activators (α-adrenoceptor agonists, collagen, and ADP) and inhibitors (β-adrenoceptor agonists, iloprost and dibutyryl cAMP) of platelet function, respectively, elicit the uptake of [⁴⁵Ca²⁺] in human platelets. It was determined that the [⁴⁵Ca²⁺] uptake methods employed reflected signal transduction events at the plasma membrane rather than absolute changes of Ca²⁺ fluxes or levels of cytosolic Ca²⁺. In the present study, basal (unstimulated) [⁴⁵Ca²⁺] uptake by platelets from both type I and type II diabetic patients was significantly enhanced when compared to age-matched controls. When basal values were subtracted from stimulated values, there were highly significant decreases in [⁴⁵Ca²⁺] uptake in platelets from type I diabetic patients compared to controls when stimulated with adrenaline, isoprenaline, noradrenaline, collagen, A23187, or iloprost. In contrast, when basal values were subtracted from stimulated values there were significant increases in [⁴⁵Ca²⁺] uptake by platelets from type II diabetic patients when stimulated with adrenaline, isoprenaline, noradrenaline, A23187, iloprost, and collagen. It is concluded that in type I and type II DM there are differential alterations in [⁴⁵Ca²⁺] sequestration linked to inhibitors and stimulators of platelet activation. These data indicate that the hyperaggregability of platelets that is associated with both type I and type II DM may be due to an aetiology other than Ca²⁺ mobilization linked to signal transduction. Copyright (C) 2000 Elsevier Science Inc.