title: Glucagon-like peptide 1, insulin, sensory neurons, and diabetic neuropathy.
abstract: Like insulin, glucagon-like peptide 1 (GLP-1) may have direct trophic actions on the nervous system, but its potential role in supporting diabetic sensory neurons is uncertain. We identified wide expression of GLP-1 receptors on dorsal root ganglia sensory neurons of diabetic and nondiabetic mice. Exendin-4, a GLP-1 agonist, increased neurite outgrowth of adult sensory neurons in vitro. To determine the effects ofexendin-4 in comparison with continuous low- or high-dose insulin in vivo, we evaluated parallel cohorts of type 1 (streptozotocin-induced) and type 2 (db/db) mice of 2 months' diabetes duration with established neuropathy during an additional month of treatment. High-dose insulin alone reversed hyperglycemia in type 1 diabetic mice, partly reversed thermal sensory loss, improved epidermal innervation but failed to reverse electrophysiological abnormalities. Exendin-4 improved both sensory electrophysiology and behavioral sensory loss. Low-dose insulin was ineffective. In type 2 diabetes, hyperglycemia was uncorrected, and neither insulin nor exendin-4 reversed sensory electrophysiology, sensory behavior, or loss of epidermal axons. However, exendin-4 alone improved motor electrophysiology. Receptor for advanced glycosylated end products and nuclear factor-κB neuronal expression were not significantly altered by diabetes or treatment. Taken together, these results suggest that although GLP-1 agonists and insulin alone are insufficient to reverse all features of diabetic neuropathy, in combination, they might benefit some aspects of established diabetic neuropathy.
authors.affiliation: Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kan
authors.forename: GuiFang
authors.initials: G
authors.lastname: Guo
authors.forename: Bhagat
authors.initials: B
authors.lastname: Singh
authors.forename: Vandana
authors.initials: V
authors.lastname: Singh
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Zochodne
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology; D003929:Diabetic Neuropathies / Q000473:pathology*; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000502:physiology*; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000502:physiology*; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology; D010455:Peptides / Q000502:physiology; D010525:Peripheral Nerves / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000187:drug effects / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014688:Venoms
chemical_list: D001786:Blood Glucose; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007328:Insulin; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat