α-Lipoic acid: Effect on glucose uptake, sorbitol pathway, and energy metabolism in experimental diabetic neuropathy

Yutaka Kishi, James D. Schmelzer, Jeffrey K. Yao, Paula J. Zollman, Kim K. Nickander, Hans J. Tritschler, Phillip Anson Low

Research output: Contribution to journalArticle

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Abstract

The peripheral nerve of experimental diabetic neuropathy (EDN) is reported to be ischemic and hypoxic, with an increased dependence on anaerobic metabolism, requiring increased energy substrate stores. When glucose stores become reduced, fiber degeneration has been reported. We evaluated glucose uptake, nerve energy metabolism, the polyol pathway, and protein kinase C (PKC) activity in EDN induced by streptozotocin. Control and diabetic rats received lipoic acid (0, 10, 25, 50, 100 mg/kg). Duration of diabetes was I month, and α-lipoic acid was administered intraperitoneally 5 times per week for the final week of the experiment. Nerve glucose uptake was reduced to 60, 37, and 30% of control values in the sciatic nerve, L5 dorsal root ganglion, and superior cervical ganglion (SCG), respectively, in rats with EDN. α-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. α-Lipoic acid had no significant effect on either energy metabolism or polyol pathway of normal nerves. In EDN, endoneurial glucose, fructose, and sorbitol were significantly increased, while myo-inositol was significantly reduced. α-Lipoic acid had a biphasic effect: it dose-dependently increased fructose, glucose, and sorbitol, peaking at 25 mg/kg, and then fell beyond that dose, and it dose- dependently increased myo-inositol. Sciatic nerve cytosolic PKC was increased in EDN. ATP, creatine phosphate, and lactate were measured in sciatic nerve and SCG. α-Lipoic acid prevented the reduction in SCG creatine phosphate. We conclude that glucose uptake is reduced in EDN and that this deficit is dose- dependently reversed by α-lipoic acid, a change associated with an improvement in peripheral nerve function.

Original languageEnglish (US)
Pages (from-to)2045-2051
Number of pages7
JournalDiabetes
Volume48
Issue number10
DOIs
StatePublished - Oct 1999

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Thioctic Acid
Sorbitol
Diabetic Neuropathies
Energy Metabolism
Glucose
Sciatic Nerve
Superior Cervical Ganglion
Inositol
Fructose
Phosphocreatine
Peripheral Nerves
Protein Kinase C
Anaerobiosis
Spinal Ganglia
Streptozocin
Lactic Acid
Adenosine Triphosphate

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Kishi, Y., Schmelzer, J. D., Yao, J. K., Zollman, P. J., Nickander, K. K., Tritschler, H. J., & Low, P. A. (1999). α-Lipoic acid: Effect on glucose uptake, sorbitol pathway, and energy metabolism in experimental diabetic neuropathy. Diabetes, 48(10), 2045-2051. https://doi.org/10.2337/diabetes.48.10.2045

α-Lipoic acid : Effect on glucose uptake, sorbitol pathway, and energy metabolism in experimental diabetic neuropathy. / Kishi, Yutaka; Schmelzer, James D.; Yao, Jeffrey K.; Zollman, Paula J.; Nickander, Kim K.; Tritschler, Hans J.; Low, Phillip Anson.

In: Diabetes, Vol. 48, No. 10, 10.1999, p. 2045-2051.

Research output: Contribution to journalArticle

Kishi, Y, Schmelzer, JD, Yao, JK, Zollman, PJ, Nickander, KK, Tritschler, HJ & Low, PA 1999, 'α-Lipoic acid: Effect on glucose uptake, sorbitol pathway, and energy metabolism in experimental diabetic neuropathy', Diabetes, vol. 48, no. 10, pp. 2045-2051. https://doi.org/10.2337/diabetes.48.10.2045
Kishi, Yutaka ; Schmelzer, James D. ; Yao, Jeffrey K. ; Zollman, Paula J. ; Nickander, Kim K. ; Tritschler, Hans J. ; Low, Phillip Anson. / α-Lipoic acid : Effect on glucose uptake, sorbitol pathway, and energy metabolism in experimental diabetic neuropathy. In: Diabetes. 1999 ; Vol. 48, No. 10. pp. 2045-2051.
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N2 - The peripheral nerve of experimental diabetic neuropathy (EDN) is reported to be ischemic and hypoxic, with an increased dependence on anaerobic metabolism, requiring increased energy substrate stores. When glucose stores become reduced, fiber degeneration has been reported. We evaluated glucose uptake, nerve energy metabolism, the polyol pathway, and protein kinase C (PKC) activity in EDN induced by streptozotocin. Control and diabetic rats received lipoic acid (0, 10, 25, 50, 100 mg/kg). Duration of diabetes was I month, and α-lipoic acid was administered intraperitoneally 5 times per week for the final week of the experiment. Nerve glucose uptake was reduced to 60, 37, and 30% of control values in the sciatic nerve, L5 dorsal root ganglion, and superior cervical ganglion (SCG), respectively, in rats with EDN. α-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. α-Lipoic acid had no significant effect on either energy metabolism or polyol pathway of normal nerves. In EDN, endoneurial glucose, fructose, and sorbitol were significantly increased, while myo-inositol was significantly reduced. α-Lipoic acid had a biphasic effect: it dose-dependently increased fructose, glucose, and sorbitol, peaking at 25 mg/kg, and then fell beyond that dose, and it dose- dependently increased myo-inositol. Sciatic nerve cytosolic PKC was increased in EDN. ATP, creatine phosphate, and lactate were measured in sciatic nerve and SCG. α-Lipoic acid prevented the reduction in SCG creatine phosphate. We conclude that glucose uptake is reduced in EDN and that this deficit is dose- dependently reversed by α-lipoic acid, a change associated with an improvement in peripheral nerve function.

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