Yazarlar |
Doç. Dr. Mustafa KAN
Kırşehir Ahi Evran Üniversitesi |
GuiFang Guo
|
Bhagat Singh
|
Vandana Singh
|
Douglas W. Zochodne
|
Özet |
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. |
Anahtar Kelimeler |
Diabetes mellitus | Diabetic neuropathy | Exendin-4 | Glucagon-like peptide 1 | Insulin | Polyneuropathy |
Makale Türü | Özgün Makale |
Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale |
Dergi Adı | JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY |
Dergi ISSN | 0022-3069 |
Dergi Grubu | Q4 |
Makale Dili | İngilizce |
Basım Tarihi | 06-2012 |
Cilt No | 71 |
Sayı | 6 |
Sayfalar | 494 / 510 |
Doi Numarası | 10.1097/NEN.0b013e3182580673 |
Atıf Sayıları | |
WoS | 62 |