Altered cellular Ca2+ and Na+ transport in diabetes mellitus.
Platelet intracellular Ca2+ concentration ([Ca2+]i) and its response to stimuli (ADP and thrombin) were studied in 15 insulin-dependent and 22 non-insulin-dependent diabetes mellitus patients with the fluorescent probe Fura 2. The activity of Ca2(+)-ATPase and Na(+)-K(+)-ATPase, membrane fluidity, and cholesterol and phospholipid content were also determined in platelet membranes. Compared with control subjects, diabetic patients showed 1) increased platelet [Ca2+]i in the resting state, 2) higher Ca2+ levels after stimulation with thrombin and ADP, due entirely to increased resting concentrations, 3) reduced activity of Na(+)-K(+)-ATPase, 4) increased activity of Ca2(+)-ATPase, 5) higher fluidity of the platelet membrane, and 6) increased membrane concentration of total phospholipids. Na(+)-K(+)-ATPase activity was inversely related to platelet [Ca2+]i in each group studied, whereas Ca2(+)-ATPase activity was positively correlated with intracellular Ca2+ levels. The data obtained in diabetic subjects suggest an abnormality in Ca2+ and Na+ transport across the platelet membrane that might be responsible for the reported platelet hyperreactivity to stimuli in diabetes.
Mazzanti
L
L
Institute of Biochemistry, Ancona, Italy.
Rabini
R A
RA
Faloia
E
E
Fumelli
P
P
Bertoli
E
E
De Pirro
R
R
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D000252:Calcium-Transporting ATPases / Q000097:blood; D002784:Cholesterol / Q000097:blood; D003600:Cytosol; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000097:blood; D008875:Middle Aged; D010743:Phospholipids / Q000097:blood; D012016:Reference Values; D012964:Sodium / Q000097:blood*; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood; D013917:Thrombin / Q000502:physiology; D014280:Triglycerides / Q000097:blood
D008563:Membrane Lipids; D010743:Phospholipids; D014280:Triglycerides; D000244:Adenosine Diphosphate; D002784:Cholesterol; D012964:Sodium; D013917:Thrombin; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium