The Effect of Diabetes, Insulin and Wallerian Degeneration on Leucine Metabolism of Isolated Rat Sciatic Nerves

Abstract

14C0, production and I4C incorporation into proteins was studied in isolated rat sciatic nerves during incubation with 0.1 m~-[l-'~C]leucine. Rats were made diabetic with streptozotocin. Nerves from diabetic rats incubated with glucose oxidized more [14C]leucine than controls. This difference was abolished in the presence of insulin (1 mU/ml). The effects of diabetes and insulin on leucine oxidation could not be demonstrated in the absence of glucose. Insulin stimulated the incorporation of [14C] from leucine into proteins by nerves from controls and diabetic rats.Nerves undergoing Wallerian degeneration showed a marked increase in DNA content and stimulated incorporation of [14C]leucine into proteins. 14C02 production from leucine proceeded at 753; of the rate observed in intact nerves. Neither insulin nor diabetes affected leucine metabolism in degenerating nerves.Neither the extracellular space nor the concentration of free amino acids were significantly different in nerves obtained from control and diabetic rats, except for lower glutamine content in the latter. I n oitro leucine metabolism of nerves is affected by diabetes, insulin and the integrity of the axon. The Schwann cell is suggested as a possible site of the observed changes in leucine metabolism.

Effect of streptozotocin on erythrocyte and retinal superoxide dismutase

“…Diabetic animals were included in the experiments only if the concentration of glucose in plasma was greater than 300 mg per 100 ml and if the animals either lost weight or gained less than 1 g per day. Previous studies from this laboratory [16] reported a weight gain of 6.75 _+ 0.28 g/day for 16 normal rats of the same strain and age.…”

Insulin Reverses Enhanced Incorporation of 32P into Polyphosphoinositides in Peripheral Nerve of the Streptozotocin Diabetic Rat

“…In this regard, there is controversial information regarding actions of the hormone in vitro. Insulin has been reported to increase the rate of [3H]myo-inositol incorporation into phospholipids when added to segments of sciatic nerve (Hothersall and McLean,I979), to reverse the increased oxidation of [ ''C]leucine in diabetic rat nerves incubated with glucose (Buse et al, 1976), and to stimulate the incorporation of [ ''C]leucine into proteins of nerves from normal and diabetic rats (Buse et al, 1976;Spritz et al, 1976). On the other hand, composite glucose utilization in endoneurial preparations from rabbit sciatic nerves was found not to be subject to acute direct regulation by insulin at physiological concentrations (Greene and Winegrad, 1979).…”

Lipid Metabolism During Early Stages of Wallerian Degeneration in the Rat Sciatic Nerve

“…A marked decrease in incorporation of [ I4C]acetate occurs initially (Majno and Karnovsky, 1958;Rawlins and Smith, 197 1;Natarajan et al, 1982), but increases in incorporation of [32P]phosphate, [3H]glycerol, and [ ''C]choline have also been reported (Majno and Karnovsky, 1958;Natarajan et al, 1982). There are conflicting reports regarding metabolic alterations in protein synthesis during Wallerian degeneration; both increases (Rawlins and Smith, 1971;Buse et al, 1976;Pellegrino et al, 1986) and decreases (Porcellati, 1972;Bell et al, 1982) have been reported during the first week following nerve section. Invasion of the degenerating distal nerve stump by hematogenous cells Friede, 1984, 1986;Stoll and Muller, 1986;Muller and Minwegen, 1987) that participate in the eventual removal of degenerating myelin and other debris is clear, but This work was presented in part at the 19th Annual Meeting of Abbreviation used: SDS, sodium dodecyl sulfate.…”