Metabolism of peripheral nerve myelin in experimental diabetes.

Abstract

A B S T R A C T Previous in vitro studies of the metab-olism of the peripheral nerve have been based on incorporation of radioactive precursor into components isolated from whole nerve. In this study we have determined incorporation specifically into myelin components of peripheral nerve by isolating myelin after incubating whole nerves with lipid or protein precursors and by determining the specific activity of the components of that membrane. The effect of diabetes on such incorporation was also studied.In the rat, in vitro incorporation of DL-[1-1'C]leucine into protein components of myelin was decreased by 30-88% 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 one half that of controls. In polypeptides of mol wt 38,000-49,000, 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, [1-1'C]sodium acetate or [8H]water, into myelin components. In older animals of both species incorporation in the controls was considerably lower than in the Published previously, in part, in abstract form (1).

A defect in sodium-dependent amino acid uptake in diabetic rabbit peripheral nerve. Correction by an aldose reductase inhibitor or myo-inositol administration.

“…Reduced leucine incorporation into myelin in diabetic rodent nerve has been postulated to be a contributing factor to peripheral nerve hypomyelination in diabetes (47,48). This defect may reflect impaired amino acid uptake by diabetic peripheral nerve in vitro (while this defect appeared to be partially insulin sensitive, pharmacological concentrations ofinsulin far in excess of those employed in the present report were required (46)).…”

Sodium- and energy-dependent uptake of myo-inositol by rabbit peripheral nerve. Competitive inhibition by glucose and lack of an insulin effect.

“…Dixon plots of sodium-dependent uptake at 5,8,16, and 50,M myo-inositol yielded a consistent apparent Ki(glucose) of 37.8±2.2 (n = 6) (Fig. 4).…”

“…Contrary to previous views (1,2), circulating insulin does not primarily regulate peripheral nerve glucose and energy metabolism (3). Consequently, experimental diabetes does not impair glucose-derived energy production in peripheral nerve (4) although subtle insulin-sensitive metabolic perturbations in diabetic peripheral nerve have been described (4,5). Recent attention has focussed on possible direct pathogenetic effects of hyperglycemia on peripheral nerve metabolism (6,7).…”

Peripheral nerve structures of experimental diabetes rats and the effect of insulin treatment.

“…Field (1966) and Spritz et al (1975) indicated insufficient metabolism of myelin sheaths of Schwann cells. Delayed axoplasmic flow as an axonal dysfunction was detected in streptozotocin diabetes rats (Schmidt et al 1975).…”