Effect of experimental diabetes on the susceptibility of myelin proteins to proteolysis.

Abstract

To investigate abnormalities in peripheral nerve myelin in experimental diabetes, we studied the effects of the proteolytic enzymes trypsin and alpha-chymotrypsin on the proteins of this membrane, obtained from the sciatic nerves of normal rats and from animals made diabetic with streptozotocin. The dominant effect of the proteolytic enzymes was to incompletely degrade the major membrane protein (mol. wt. 28,000), with the appearance of new protein (mol. wt. 20,000). Using myelin isolated from the nerves of diabetic animals, the reaction was approximately one-half that of the controls (P less than 0.01) for both enzymes. When, however, the myelin protein affected by trypsin and chymotrypsin was isolated from the membrane and then incubated with the proteolytic enzyme, its proteolysis was complete and took place at the same rate in the diabetic animals and controls. These findings suggest that, in this model of experimental diabetes, there is an alteration in the structure of peripheral nerve myelin that inhibits interaction between the protein in the membrane bilayer and two water soluble proteolytic enzymes. This alteration could not be demonstrated in protein isolated from the membrane, suggesting that the change relates to the interaction of the protein and other components of myelin, rather than to chemical alteration in the protein per se.