Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy

Exp Neurol. 2007 Feb;203(2):293-301. doi: 10.1016/j.expneurol.2006.09.028. Epub 2006 Nov 22.


Pyridoxine (vitamin B6) intoxicated rodents develop a peripheral neuropathy characterized by sensory nerve conduction deficits associated with disturbances of nerve fiber geometry and axonal atrophy. To investigate the possibility that glucagon-like peptide-1 (7-36)-amide (GLP-1) receptor agonism may influence axonal structure and function through neuroprotection neurotrophic support, effects of GLP-1 and its long acting analog, Exendin-4 (Ex4) treatment on pyridoxine-induced peripheral neuropathy were examined in rats using behavioral and morphometric techniques. GLP-1 is an endogenous insulinotropic peptide secreted from the gut in response to the presence of food. GLP-1 receptors (GLP-1R) are coupled to the cAMP second messenger pathway, and are expressed widely throughout neural tissues of humans and rodents. Recent studies have established that GLP-1 and Ex4, have multiple synergistic effects on glucose-dependent insulin secretion pathways of pancreatic beta-cells and on neural plasticity. Data reported here suggest that clinically relevant doses of GLP-1 and Ex4 may offer some protection against the sensory peripheral neuropathy induced by pyridoxine. Our findings suggest a potential role for these peptides in the treatment of neuropathies, including that associated with type II diabetes mellitus.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Behavior, Animal / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Exenatide
  • Ganglia, Spinal / pathology
  • Glucagon-Like Peptide 1 / physiology*
  • Glucagon-Like Peptide-1 Receptor
  • Male
  • Molecular Sequence Data
  • Muscle Tonus / physiology
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / pathology
  • Neurons, Afferent*
  • Neuroprotective Agents*
  • Peptides / therapeutic use*
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / prevention & control*
  • Postural Balance / drug effects
  • Pyridoxine*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucagon / agonists*
  • Sciatic Nerve / pathology
  • Venoms / therapeutic use*
  • Vitamins*


  • Blood Glucose
  • GLP1R protein, human
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Neuroprotective Agents
  • Peptides
  • Receptors, Glucagon
  • Venoms
  • Vitamins
  • Glucagon-Like Peptide 1
  • Exenatide
  • Pyridoxine