Glucose Uptake And Energy Metabolism

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a-Lipoic acid has a number of actions in addition to its antioxidant properties. These include its effect on glucose uptake. We therefore evaluated glucose uptake, nerve energy metabolism, and the polyol pathway in EDN induced by streptozotocin. Control and diabetic rats received lipoic acid at various doses (0, 10, 25, 50, and 100 mg/kg). Duration of diabetes was 1 month, and a-lipoic acid was administered intraperitoneally 5 times during the final week of the experiment. Nerve glucose uptake was reduced to 60%, 37% and 30% of control values in the sciatic nerve, L5 DRG, and superior cervical ganglion, respectively, in EDN. a-Lipoic acid supplementation had no effect on glucose uptake in normal nerves at any dose but reversed the deficit in EDN, with a threshold between 10 and 25 mg/kg.

Endoneurial glucose, fructose, sorbitol, and myo-inositol were measured in sciatic nerve and L5 DRG. ATP, creatine phosphate, and lactate were measured in sciatic nerve and superior cervical ganglion. a-Lipoic acid had no significant effect on either energy metabolism or polyol pathway of normal nerves. In contrast, it significantly increased glucose, fructose, and sorbitol but paradoxically increased, rather than reduced, endoneurial myo-inositol. a-Lipoic acid prevented the reduction in superior cervical ganglion creatine phosphate. We conclude that glucose uptake is reduced in EDN and that this deficit is dose-dependently reversed by a-lipoic acid, a change associated with an improvement in peripheral nerve function, possibly by improving energy metabolism in ischemic nerve and by increasing endoneurial myo-inositol.

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