Intracellular calcium homeostasis in platelets of patients with type 2 diabetes mellitus (DM) has been reported to be altered, leading to enhanced and sustained calcium responses that result in increased adhesiveness and spontaneous aggregation. An impaired calcium extrusion by the plasma membrane calcium-ATPase (PMCA) has been shown to be especially relevant in type 2 diabetic subjects, maintaining an elevated cytosolic free calcium concentration that results in platelet hypersensitivity. Treatment of platelets from diabetic patients with 300 U/mL catalase or 5 mM D-mannitol, which mainly prevent oxidative stress mediated by H₂O₂ and hydroxyl radicals, respectively, increases calcium clearance by PMCA after treatment with thapsigargin (TG) in combination with ionomycin (Iono). In contrast, treatment with 1 mM trolox, a scavenger of ONOO^-, did not alter TG + Ionoinduced response. Catalase and D-mannitol reversed the enhanced tyrosine phosphorylation of PMCA induced by TG + Iono in diabetic patients. These findings suggest that endogenously generated oxidants are involved in the impaired platelet PMCA activity observed in type 2 diabetic patients.

Supported by MEC-DGI grant BFU2004-00165.