Differential alterations of spontaneous and stimulated 45Ca(2+) uptake by platelets from patients with type I and type II diabetes mellitus.

摘要

Diabetes mellitus (DM) is associated with hyperaggregability of platelets. Although the mechanisms underlying this abnormality remain unknown, Ca(2+) imbalance has been implicated. Both activators (alpha-adrenoceptor agonists, collagen, and ADP) and inhibitors (beta-adrenoceptor agonists, iloprost and dibutyryl cAMP) of platelet function, respectively, elicit the uptake of [45Ca(2+)] in human platelets. It was determined that the [45Ca(2+)] uptake methods employed reflected signal transduction events at the plasma membrane rather than absolute changes of Ca(2+) fluxes or levels of cytosolic Ca(2+). In the present study, basal (unstimulated) [45Ca(2+)] 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 [45Ca(2+)] 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 [45Ca(2+)] 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 [45Ca(2+)] 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 Ca(2+) mobilization linked to signal transduction.