Decrease of nerve Na+,K+-ATPase activity in the pathogenesis of human diabetic neuropathy

doi:10.1016/0022-510X(93)90268-4

Journal of the Neurological Sciences

Volume 120, Issue 2, 15 December 1993, Pages 159-167

https://doi.org/10.1016/0022-510X(93)90268-4 Get rights and content

Abstract

A decrease in Na⁺,K⁺-ATPase activity is claimed to play a central role in the pathogenesis of electrophysiological and morphological abnormalities that characterize the neuropathic complications in different animal models of diabetes mellitus. The peripheral nerves from 17 patients with either type I or type II diabetes mellitus were studied to assess the importance of changes in Na⁺,K⁺-ATPase activity in chronic human diabetic neuropathy. Sixteen nerves from age- and sex-matched normal individuals, and 12 nerves from non-diabetic neuropathic subjects undergoing vascular or orthopedic surgery served as negative and positive controls, respectively. All specimens were processed blind. Ouabain-sensitive ATPase activity was measured by a modified spectrophotometric coupled-enzyme assay. Standard histology, fiber teasing and electron microscopy were used to establish the normal or neuropathological patterns of surgical material. Morphometric analysis permitted calculation of fiber density in each nerve specimen and correlation of this figure with the relevant enzymatic activity. Na⁺,K⁺-ATPase activity was approximately 59% lower in nerves from diabetic patients than in normal controls (P < 0.01) and approximately 38% lower in nerves from non-diabetic patients with neuropathy (P < 0.01). Although nerves from both neuropathic conditions had significantly fewer fibers than those from normal individuals (diabetic −33%, and non-diabetic −22%), the decreases in Na⁺,K⁺-ATPase activity and fiber density were not correlated only in specimens from diabetic patients (r² = 0.096; P = 0.22). Taken together with data from experimental animal models, these results suggest that the reduction in Na⁺,K⁺-ATPase activity in diabetic nerves is not an epiphenomenon secondary to fiber loss; rather, it may be an important factor in the pathogenesis and self-maintenance of human diabetic neuropathy.

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^☆: Presented in part at the 42nd Annual Meeting of the American Academy of Neurology, April 30 to May 6, 1990, Miami Beach, FL, USA.

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Research articleDecrease of nerve Na+,K+-ATPase activity in the pathogenesis of human diabetic neuropathy☆

Abstract

J. Biol. Chem.

Life Sci.

Metabolism

Neurosci. Res.

J. Neurol. Sci.

Exp. Neurol.

Neurosci. Lett.

Biochim. Biophys. Acta

J. Biol. Chem.

Brain Res.

Biochim. Biophys. Acta

J. Neurol. Sci.

Brain Res.

Diabetes Res. Clin. Pract.

Metabolism

Effect of Na+,K+-ATPase modifiers on high-affinity ouabain binding determined by quantitative autoradiography

J. Neurosci. Res.

Erythrocyte sodium fluxes, ouabain binding sites, and Na+,K+-ATPase activity in hyperthyroidism

Metabolism

Phosphorylation of the catalytic subunit of Na+,K+-ATPase inhibits the activity of the enzyme

Sodium-potassium-ATPase activity is influenced by ethnic origin and not by obesity

N. Engl. J. Med.

ATPase activity defects in alloxan-induced diabetic sciatic nerve recovered by ganglioside treatment

Diabetes

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Effect of ganglioside treatment

Diabetes

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Diabetologia

Reversible and irreversible nodal dysfunction in diabetic neuropathy

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Hypoxic neuropathy: does hypoxia play a role in diabetic neuropathy?

The 1988 Robert Wartenberg Lecture

Neurology

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Brain

Fiber loss is primary and multifocal in sural nerves in diabetic polyneuropathy

Ann. Neurol.

Changed distribution of sodium channels along demyelinated axons

Effects of dialysis and transplantation on red cell Na pump function in renal failure

Nephron

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Effect of ganglioside treatment on axonal transport of cytoskeletal proteins

Diabetes

Ganglioside treatment reverses the diabetes-induced decrease in ouabain binding in rat sciatic nerve

Characteristics of learning and memory in streptozocin-induced diabetic mice

Diabetes

Sodium-potassium-ATPase activity in the dorsal root ganglia of rats with streptozotocin-induced diabetes

Diabetologia

Impaired rat sciatic nerve sodium-potassium adenosine triphosphatase in acute streptozotocin diabetes and its correction by dietary myo-inositol supplementation

J. Clin. Invest.

Effects of acute experimental diabetes on composite energy metabolism in peripheral nerve axons and Schwann cells

Diabetes

Sorbitol, phosphoinositides, and sodium potassium-ATPase in the pathogenesis of diabetic complications

N. Engl. J. Med.

Research article
Decrease of nerve Na⁺,K⁺-ATPase activity in the pathogenesis of human diabetic neuropathy☆

Effect of Na⁺,K⁺-ATPase modifiers on high-affinity ouabain binding determined by quantitative autoradiography

Erythrocyte sodium fluxes, ouabain binding sites, and Na⁺,K⁺-ATPase activity in hyperthyroidism

Phosphorylation of the catalytic subunit of Na⁺,K⁺-ATPase inhibits the activity of the enzyme