Although
diabetic polyneuropathy (
DPN) is a frequent
diabetic complication, no effective therapeutic approach has been established.
Glucagon is a crucial
hormone for
glucose homeostasis but has pleiotropic effects, including
neuroprotective effects in the central nervous system. However, the importance of
glucagon in the peripheral nervous system (PNS) has not been clarified. Here, we hypothesized that
glucagon might have a neuroprotective function in the PNS. The immortalized rat dorsal root ganglion (DRG) neuronal cell line 50B11 was treated with
methylglyoxal (MG) to mimic an in vitro
DPN model. The cells were cultured with or without
glucagon or MG. Neurotoxicity, survival, apoptosis, neurite projection, cyclic
adenosine monophosphate (cAMP), and
protein kinase A (PKA) were examined.
Glucagon had no cytotoxicity and rescued the cells from neurotoxicity. Cell survival was increased by
glucagon. The ratio of apoptotic cells, which was increased by MG, was reduced by
glucagon. Neurite outgrowth was accelerated in
glucagon-treated cells.
Cyclic AMP and PKA accumulated in the cells after
glucagon stimulation. In conclusion,
glucagon protected the DRG neuronal cells from MG-induced cellular stress. The cAMP/PKA pathway may have significant roles in those protective effects of
glucagon.
Glucagon may be a potential target for the treatment of
DPN.