期刊
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
卷 71, 期 6, 页码 494-510出版社
OXFORD UNIV PRESS INC
DOI: 10.1097/NEN.0b013e3182580673
关键词
Diabetes mellitus; Diabetic neuropathy; Exendin-4; Glucagon-like peptide 1; Insulin; Polyneuropathy
资金
- Canadian Institutes of Health Research
- Canadian Diabetes Association
- Alberta Innovates-Health Solutions
- Alberta Heritage Foundation for Medical Research
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 of exendin-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-kappa B 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.
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