Altered platelet membrane dynamic properties in type 1 diabetes.
A modified platelet response to aggregating stimuli is supposed to play a role in the pathogenesis of diabetic macroangiopathy. We studied the fluidity and microheterogeneity of the external surface of the platelet membrane and the activities of the plasma membrane Na+-K+-ATPase and Ca2+-ATPase in 21 men with type 1 diabetes and in 20 control subjects before and after in vitro thrombin addition. In the resting state, platelets from type 1 diabetic patients showed an increased fluidity and microheterogeneity of the platelet membrane, a higher Ca2+-ATPase activity, and a reduced Na+-K+-ATPase activity in comparison with platelets from healthy subjects. The fatty acid composition was also modified, with increased C 16:1 and decreased C 18:0 content. Control cells incubated with thrombin showed a modification of the membrane parameters opposite to the response observed in type 1 cells after the stimulation. The incubation of control platelets in the resting state with high concentrations of glucose modified the fluidity of the plasma membrane Na+-K+-ATPase and Ca2+-ATPase activities in an opposite way in comparison with the alterations observed in type 1 platelets. This study suggests that in type 1 diabetic patients, the platelet membrane responds to activation with a molecular remodeling different from the response of healthy subjects. The abnormal organization of the membrane might contribute to the altered platelet functions in type 1 diabetic patients, but acute exposure to high glucose levels does not seem able to modify the platelet membrane in the way observed in type 1 diabetes.
Mazzanti
L
L
Institute of Biochemistry, University of Ancona, INRCA, Italy. mazzanti@popcsi.unian.it
Rabini
R A
RA
Fumelli
P
P
Martarelli
D
D
Staffolani
R
R
Salvolini
E
E
Curatola
G
G
D000328:Adult; D001792:Blood Platelets / Q000502:physiology / Q000648:ultrastructure*; D000252:Calcium-Transporting ATPases / Q000097:blood; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004161:Diphenylhexatriene / Q000031:analogs & derivatives; D005227:Fatty Acids / Q000097:blood; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D008297:Male; D008560:Membrane Fluidity; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood
D005227:Fatty Acids; D005456:Fluorescent Dyes; D004161:Diphenylhexatriene; C033628:1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose