Metabolism of peripheral nerve myelin in experimental diabetes

Abstract

In the rat, in vitro incorporation of DL [1 14C]leucine into protein components of myelin was decreased by 30 to 88% in diabetic animals as compared to controls. The major polypeptide constituent of rat sciatic nerve myelin (mol wt 28,000; 58.5% of total mass of proteins) was not labeled in either the diabetic or the control group. In diabetes, incorporation rate into a polypeptide of mol wt 23,000, which constitutes 21% of total mass, was approximately 1/2 that of controls. In polypeptides of mol wt 38,000 to 49,000, which are heavily labeled in normal animals, but constitute only about 5% of total mass of proteins, depression of incorporation was even more marked in the diabetics. While these marked differences in incorporation between diabetic and control animals were observed, the amount of protein and its distribution among the constituent polypeptides was the same in both groups. In young rats made diabetic with streptozotocin and young rabbits made diabetic with alloxan, there was a lower rate of incorporation of the lipid precursors, [1 14C]sodium acetate or [3H]water, into myelin components. In older animals of both species incorporation in the controls was considerably lower than in the young animals, and the effect of diabetes was no longer apparent. In non diabetic animals, the in vitro addition of insulin (10-7 M) stimulated incorporation of DL [1 14C]leucine into myelin proteins 1.6 to 3.1 times that of controls. This stimulation by insulin in vitro was not seen in diabetic animals. In animals in which diabetes had spontaneously recovered, however, incorporation rate in the in vitro experiments approached that of controls and were significantly above that in animals whose diabetes persisted. Since myelin is the plasma membrane of the Schwann cell, these studies provide evidence that the Schwann cell is affected by insulin and that some aspects of the metabolism of myelin are altered in insulin deficient states.