Effects of Acute Experimental Diabetes on Composite Energy Metabolism in Peripheral Nerve Axons and Schwann Cells

Abstract

Rabbit tibial nerve fascicle and endoneurial preparations were used to study the effects of alloxan diabetes on composite energy metabolism in peripheral nerve axons and Schwann cells. Glucose was preferentially used for energy provision in fascicle and endoneurial preparations from diabetic rabbits (despite very high endogenous fructose concentrations) and respiration provided the preponderant fraction of their energy requirements. Diabetic fascicles incubated with 20 mM glucose maintained a steady state of energy metabolism for 2 h, as assessed by O2 uptake , ATP levels, and P-creatine/creatine ratio. Their steadystate rate of energy utilization was estimated from the theoretical yield of ATP from the rates of glucose utilization required to sustain the steady state O2 uptake and lactate production. This was equivalent to the use of 117 mmol ATP/kg/h, a value 26% lower than in normal fascicles, but the ATP levels and P-creatine/creatine ratios in diabetic fascicles were unaltered. Diabetic endoneurium maintained a near steady state of energy metabolism when incubated with 5 mM glucose; its rate of energy utilization was 31% lower than in normal endoneurium, although their ATP levels and P-creatine/creatine ratios were similar. Experimental diabetes results in a striking decrease in the composite steady-state rate of energy utilization in axons and Schwann cells, suggesting that the rates of specific energy requiring processes operative in normal nerve are decreased. Diabetic fascicles and endoneurium had significantly decreased myo-inositol and creatine + P-creatine concentrations, suggesting that the maintenance of the normal intracellular/extracellular gradients of myo-inositol and creatine is impaired. The rate of energy utilization in normal endoneurium was not altered by incubation with 20 mM glucose for 2 h. Insulin (100 μU/ml) did not increase the rate of energy utilization in diabetic endoneurium incubated with glucose.