Aldose reductase inhibition alters nodal Na+ currents and nerve conduction in human diabetics.

Full Abstract

BACKGROUND: In diabetic nerves, activation of the polyol pathway via an aldose reductase and the resulting impairment of the Na(+)-K(+) pump would lead to a decreased transaxonal Na+ gradient and thereby reduced nodal Na+ currents. OBJECTIVE: To investigate whether the aldose reductase inhibitor (ARI) epalrestat improves nodal Na+ currents and nerve conduction in human diabetic neuropathy. METHODS: The authors conducted a 6-month, open clinical trial with an ARI, epalrestat, in 30 patients with mild-to-moderate diabetic neuropathy. The latent addition technique and measurements of the strength-duration time constant were used to estimate nodal persistent Na+ currents in median motor axons. Excitability testing and extensive nerve conduction studies including F-wave analyses were performed before and 1 and 6 months after the initiation of treatment with oral epalrestat. RESULTS: Within a month of the start of treatment, there was a significant improvement in nerve conduction, particularly in conduction times across the carpal tunnel and F-wave latencies. The results of latent addition (p < 0.05) and strength-duration time constant (p = 0.06) suggested increased nodal persistent Na+ currents. At 6 months, nerve conduction continued to improve. CONCLUSIONS: Aldose reductase pathway inhibition could rapidly increase nodal Na+ currents and thereby improve the slowing of nerve conduction, presumably because of a restoration of the membranous Na+ gradient.

Author information

Author/s: Misawa, S (S); Kuwabara, S (S); Kanai, K (K); Tamura, N (N); Nakata, M (M); Sawai, S (S); Yagui, K (K); Hattori, T (T);

Affiliation: Department of Neurology, Chiba University School of Medicine, Chiba, Japan. sonoko.m(-atsign-)mb.infoweb.ne.jp

Journal and publication information

Publication Type: Clinical Trial; Journal Article

Journal: Neurology (Neurology), published in United States. (Language: eng)

Reference: 2006-May; vol 66 (issue 10) : pp 1545-9

Dates: Created 2006/05/23; Completed 2006/06/28; Revised 2006/11/15;

PMID: 16717216, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult
Aged
Aged, 80 and over
Aldehyde Reductase - antagonists & inhibitors
Carpal Tunnel Syndrome - drug therapy; etiology; physiopathology
Diabetes Mellitus, Type 1 - drug therapy; enzymology; physiopathology
Diabetes Mellitus, Type 2 - drug therapy; enzymology; physiopathology
Diabetic Neuropathies - drug therapy; enzymology; physiopathology
Female
Hemoglobin A, Glycosylated - analysis
Humans
Hypoglycemic Agents - pharmacology; therapeutic use

Hypoglycemic Agents - pharmacology; therapeutic use
Insulin - therapeutic use
Ion Transport - drug effects
Male
Median Nerve - physiopathology
Middle Aged
Neural Conduction - drug effects
Reaction Time - drug effects
Rhodanine - analogs & derivatives; pharmacology; therapeutic use
Sodium - metabolism
Sodium Channels - drug effects; metabolism
Thiazolidines

Associated Chemicals: Hemoglobin A, Glycosylated (0) ; Hypoglycemic Agents (0) ; Sodium Channels (0) ; Thiazolidines (0) ; Insulin (11061-68-0) ; Rhodanine (141-84-4) ; Sodium (7440-23-5) ; ONO 2235 (82159-09-9) ; Aldehyde Reductase (EC 1.1.1.21)

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