DIABETES-MELLITUS ALTERS THE EFFECT OF PEPTIDE AND PROTEIN LIGANDS ONMEMBRANE FLUIDITY OF BLOOD-PLATELETS

The increased nonenzymatic glycosylation of platelet membrane proteins has been suggested to underlie platelet hypersensitivity in diabetes and the relationship of this to the reduced membrane lipid fluidity ha s been reported. As the modulation in membrane fluidity may determine the degree of accessibility of membrane receptors, the consequent alte rations in membrane lipid-protein interactions in diabetes mellitus ma y also underlie the differentiated effects of various thrombotic and f ibrinolytic agents on platelet membrane lipid bilayer. In the present study we employed electron paramagnetic resonance and fluorescence spe ctroscopy to explore the ligand-induced platelet membrane fluidity cha nges in diabetic state, i.e. under conditions when the membrane archit ecture is considerably altered. The yield of the excimer formation of pyrenemaleimide (PM), which depends directly upon the collisional rate and distances between molecules, was elevated in diabetic platelet me mbranes, thus pointing to the occurrence of some constraints in the st ructure/conformation of platelet membrane proteins in diabetes mellitu s. Such an immobilization of PM was accompanied by the significant ele vation in membrane protein glycation in diabetic platelets. The effect s of various interacting ligands on platelet membrane fluidity were si gnificantly lower in diabetic platelets, and the differences were much more distinct at the lower depths of a lipid bilayer. Nevertheless, t he alterations in membrane lipid fluidity observed upon the interactio n of a given ligand occurred with an approximately equal frequency in control and diabetic platelets. Moreover, the probability that these a lterations were less profound in diabetic platelets was the same for a ll types of ligands studied. In diabetic patients the interaction of R GDS and tissue-type plasminogen activator with platelet membranes resu lted in much smaller reductions of the h(+1)/h(0) parameters in 5-DOXY L-Ste acid-labelled platelets, thus indicating a lesser rigidization o f membrane lipid bilayer in diabetes. Likewise, the fluidizing effect of both fibrinogen itself and fibrinogen-derived peptides containing g amma-chain carboxy-terminal sequence H-12-V was less pronounced in dia betic platelet membranes.