Differential alterations of spontaneous and stimulated Ca-45(2+) uptake byplatelets 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+ im balance 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 [ Ca-45(2+)] in human platelets. It was determined that the [Ca-45(2+)] uptak e methods employed reflected signal transduction events at the plasma membr ane rather than absolute changes of Ca2+ fluxes or levels of cytosolic Ca2. In the present study, basal (unstimulated) [Ca-45(2+)] uptake by platelet s from both type I and type II diabetic patients was significantly enhanced when compared to age-matched controls. When basal values were subtracted f rom stimulated values, there were highly significant decreases in [Ca-45(2)] uptake in platelets from type I diabetic patients compared to controls w hen stimulated with adrenaline, isoprenaline, noradrenaline, collagen, A231 87, or iloprost. In contrast, when basal values were subtracted from stimul ated values there were significant increases in [Ca-45(2+)] uptake by plate lets from type II diabetic patients when stimulated with adrenaline, isopre naline, noradrenaline, A23187, iloprost, and collagen. It is concluded that in type I and type II DM there are differential alterations in [Ca-45(2+)] sequestration linked to inhibitors and stimulators of platelet activation. These data indicate that the hyperaggregability of platelets that is assoc iated with both type I and type II DM may be due to an aetiology other than Ca2+ mobilization linked to signal transduction. (C) 2000 Elsevier Science Inc.