Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy.
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.
Perry
TracyAnn
T
Drug Design and Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Room 2C13, Gerontology Research Center, 5600 Nathan Shock Dr., Baltimore, MD 21224, USA.
Holloway
Harold W
HW
Weerasuriya
Ananda
A
Mouton
Peter R
PR
Duffy
Kara
K
Mattison
Julie A
JA
Greig
Nigel H
NH
D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D000077270:Exenatide; D005727:Ganglia, Spinal / Q000473:pathology; D052216:Glucagon-Like Peptide 1 / Q000502:physiology*; D000067757:Glucagon-Like Peptide-1 Receptor; D008297:Male; D008969:Molecular Sequence Data; D009129:Muscle Tonus / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009475:Neurons, Afferent; D018696:Neuroprotective Agents; D010455:Peptides / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D004856:Postural Balance / Q000187:drug effects; D011736:Pyridoxine; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists*; D012584:Sciatic Nerve / Q000473:pathology; D014688:Venoms / Q000627:therapeutic use*; D014815:Vitamins
D001786:Blood Glucose; C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D018696:Neuroprotective Agents; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D014815:Vitamins; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D011736:Pyridoxine