title: Aldose reductase inhibition alters nodal Na+ currents and nerve conduction in human diabetics.
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.
authors.affiliation: Department of Neurology, Chiba University School of Medicine, Chiba, Japan. sonoko.m@mb.infoweb.ne.jp
authors.forename: S
authors.initials: S
authors.lastname: Misawa
authors.forename: S
authors.initials: S
authors.lastname: Kuwabara
authors.forename: K
authors.initials: K
authors.lastname: Kanai
authors.forename: N
authors.initials: N
authors.lastname: Tamura
authors.forename: M
authors.initials: M
authors.lastname: Nakata
authors.forename: S
authors.initials: S
authors.lastname: Sawai
authors.forename: K
authors.initials: K
authors.lastname: Yagui
authors.forename: T
authors.initials: T
authors.lastname: Hattori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D002349:Carpal Tunnel Syndrome / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D017136:Ion Transport / Q000187:drug effects*; D008297:Male; D008475:Median Nerve / Q000503:physiopathology; D008875:Middle Aged; D009431:Neural Conduction / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D053778:Thiazolidines
chemical_list: D000449:Aldehyde Reductase; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D012236:Rhodanine; D012964:Sodium; D015222:Sodium Channels; D053778:Thiazolidines; C038131:epalrestat