Differential alterations of spontaneous and stimulated 45Ca(2+) 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, 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.
Gill
J K
JK
Department of Chemical Pathology and Human Metabolism, Royal Free Hospital and School of Medicine, University of London, London, UK.
Fonseca
V
V
Dandona
P
P
Mikhailidis
D P
DP
Angelini
G D
GD
Jeremy
J Y
JY
D000328:Adult; D017668:Age of Onset; D000368:Aged; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D002132:Calcium Radioisotopes; D003094:Collagen / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D012016:Reference Values
D001786:Blood Glucose; D000001:Calcimycin; D002118:Calcium; D002132:Calcium Radioisotopes; D003094:Collagen; D004837:Epinephrine; D006442:Glycated Hemoglobin; D016285:Iloprost; D007545:Isoproterenol; D009638:Norepinephrine