DOES REDUCED MEMBRANE LIPID FLUIDITY UNDERLIE THE ALTERED THROMBIN-INDUCED EXPRESSION OF INTEGRIN ALPHA(IIB)BETA(3) AND PADGEM-140 IN MEMBRANES OF PLATELETS FROM DIABETIC JUVENILES

In diabetic patients, where the membrane lipid microviscosity of blood platelets is altered, the availability of platelet membrane receptors may change concomitantly, Platelet hypersensitivity in diabetic subje cts was previously hypothesized to result from the nonenzymatic glycos ylation-induced loss in platelet membrane fluidity, In our present stu dy juvenile type 1 diabetic subjects were compared with their relevant controls with respect to thrombin-stimulated platelet activation in r elation to glycation-induced impairments of platelet membrane dynamics , Our results indicate that: (a) the mean steady-state fluorescence po larization (p) of both 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-anili no-8-naphthalenesulphonate (ANS) in membranes from diabetic subjects w ere significantly greater than for control subjects, thus indicating r educed membrane lipid fluidity in diabetic platelets in various membra ne regions; (b) the significantly higher [H-3]NaBH4 reduction, indicat ing the increased attachment of glucose to protein amino groups, was a ttributed to the proteins extracted from diabetic platelet membranes; (c) CD62-positive resting platelets were not significantly more abunda nt in diabetic patients; (d) basically, unaltered amounts of PADGEM-14 0 membrane antigen (CD62) copies were detected in resting diabetic pla telets; (e) significantly higher numbers of membrane glycoprotein B-3 were found in diabetic platelets; (f) thrombin-induced elevations in t he expression of CD61 (beta(3)) and CD62 (PADGEM-140) occurred to much higher extent in platelets of diabetic patients, thus pointing to mor e profound activation of diabetic platelets by thrombin; (g) the total amounts of platelet membrane glycoprotein beta(3) was significantly r educed in platelet lysates from diabetic subjects, We conclude that gl ycation-induced rigidization of platelet membranes might hypersensitiz e diabetic platelets to aggregating agents by rendering platelet membr ane receptors more exposed to the external environment, Thus, thrombin may bind more efficiently to the exposed glycoprotein receptors (due to glycation) in diabetic platelets, Such excessive exposure and displ acements toward the external environment might favour the accelerated shedding of some membrane proteins in diabetic platelets, We further s uggest that their subsequent replacements would render platelet intrin sic storage pools exhausted and thus, might explain the diminished tot al amount of beta(3) found in platelets of diabetic patients.