title: Ca2+ leakage rate from agonist-sensitive intracellular pools is altered in platelets from patients with type 2 diabetes.
abstract: Platelets from patients with type 2 diabetes show abnormalities in intracellular Ca(2+) homeostasis that are involved in platelet hyperaggregability and the development of thrombotic complications. Different Ca(2+) transport mechanisms have been reported to be altered in platelets from patients with type 2 diabetes, including the sarcoendoplasmic and plasma membrane Ca(2+)-ATPases, plasma membrane Ca(2+) channels, or the Na(+)/Ca(2+) exchanger. Here, we have investigated whether passive Ca(2+) leak from the stores is altered in platelets from patients with type 2 diabetes. Resting cytosolic Ca(2+) concentration ([Ca(2+)](i)) was found to be greater in platelets from patients with type 2 diabetes than in healthy controls. In a Ca(2+)-free medium, platelet stimulation with thrombin or ADP evokes a rapid and transient increase in [Ca(2+)](i) that was found to be greater in patients with diabetes than in healthy controls. Sequential or combined inhibition of Ca(2+) extrusion and Ca(2+) sequestration into the stores reduced the difference between the responses to agonists in patients with diabetes and healthy controls, although agonist-induced Ca(2+) efflux from the stores was still significantly greater in patients with diabetes. Ca(2+) leak from the dense tubular system or the acidic stores, induced by a low concentration of thapsigargin or 2,5-di-(t-butyl)-1,4-hydroquinone (TBHQ), respectively, was clearly greater in patients with diabetes than in controls, and was not significantly modified by treatment with 2-APB. These findings indicate that passive Ca(2+) leakage rate from the intracellular stores in platelets is significantly enhanced in patients with type 2 diabetes mellitus and this might explain the increased resting [Ca(2+)](i).
authors.affiliation: Unité de Recherche de Biochimie, Institute Supérieur de Biotechnologie, 5019-Monastir, Tunisia.
authors.forename: Hanene
authors.initials: H
authors.lastname: Zbidi
authors.forename: Isaac
authors.initials: I
authors.lastname: Jardin
authors.forename: Aghleb
authors.initials: A
authors.lastname: Bartegi
authors.forename: Gines M
authors.initials: GM
authors.lastname: Salido
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rosado
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D000069816:SEC Translocation Channels; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D008565:Membrane Proteins; D000069816:SEC Translocation Channels; D019831:Sodium-Calcium Exchanger; D000244:Adenosine Diphosphate; D019284:Thapsigargin; D013917:Thrombin; D002118:Calcium