Because reduced erythrocyte deformability in diabetes might be mediated by increased noneniymatic glucosylation of membrane proteins, we have isolated and studied the degree of glucosylation of spectrin, the major protein of the inner membrane surface. Spectrin was recovered from the erythrocytes of seven age-and sex-matched diabetic and nondiabetic individuals. The thiobarbituric acid (TBA) method was used to measure the glucosylation of spectrin and of 10 mg of hemoglobin from the same ceils. Increased glucosylation of both spectrin and hemoglobin was found in diabetes. Glucosylation, expressed as a ratio of TBA absorbance to protein weight was nearly three times as high for spectrin as for hemoglobin. The ratio of TBA absorbance to hemoglobin content was examined and found to be curvilinear. A reaction model with both first and second order components was fitted to the data to obtain a reaction constant. When this model and constant were used to adjust TBA ab-sorbances, spectrin's glucosylation became less than double that of hemoglobin. Spectrin forms an inner membrane network responsible for returning deformed erythrocytes to their original shape. The reported normal response to stretching of diabetic erythrocytes suggests that increased glucosylation of spectrin fails to stiffen the membrane. Some other mechanism, such as reduced phosphorylation of spectrin and other membrane proteins, may be responsible for reduced deformability of diabetic erythrocytes. But spectrin's increased glucosylation might be responsible for the increased number of poorly deformable erythrocytes found among aged diabetic erythrocytes. It may produce this effect by inhibiting the membrane protein transglutamidation responsible for removal of aged erythrocytes.

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