oxyntomodulin and Diabetic-Neuropathies

Considering the causative or contributory effects of diabetes mellitus on common neurological diseases such as polyneuropathy, stroke and dementia, modern antidiabetic drugs may be expected to reduce incidence or progression of these conditions. Nevertheless, most observed benefits have been small, except in the context of therapy for diabetes mellitus type I and new-onset polyneuropathy. Recently, semaglutide, a GLP-1 analog, has been shown to significantly reduce stroke incidence in a randomized controlled trial. Beneficial effects of antidiabetic drugs on stroke severity or outcome have been controversial, though. The level of risk conferred by diabetes mellitus, the complex pathophysiology of neurological diseases, issues of trial design, side-effects of antidiabetic drugs as well as co-medication might be interacting factors that determine the performance of antidiabetic therapy with respect to neurological outcomes. It might be speculated that early treatment of prediabetes might prevent cerebral arteriosclerosis, cognitive decline or polyneuropathy more effectively, but this remains to be demonstrated.

Topics: Dementia; Diabetes Mellitus; Diabetic Neuropathies; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; Stroke

Although diabetic polyneuropathy (DPN) is the commonest diabetic complication, its pathology remains to be clarified. As previous papers have suggested the neuroprotective effects of glucagon-like peptide-1 in DPN, the current study investigated the physiological indispensability of glucagon gene-derived peptides (GCGDPs) including glucagon-like peptide-1 in the peripheral nervous system (PNS). Neurological functions and neuropathological changes of GCGDP deficient (gcg-/-) mice were examined. The gcg-/- mice showed tactile allodynia and thermal hyperalgesia at 12-18 weeks old, followed by tactile and thermal hypoalgesia at 36 weeks old. Nerve conduction studies revealed a decrease in sensory nerve conduction velocity at 36 weeks old. Pathological findings showed a decrease in intraepidermal nerve fiber densities. Electron microscopy revealed a decrease in circularity and an increase in g-ratio of myelinated fibers and a decrease of unmyelinated fibers in the sural nerves of the gcg-/- mice. Effects of glucagon on neurite outgrowth were examined using an ex vivo culture of dorsal root ganglia. A supraphysiological concentration of glucagon promoted neurite outgrowth. In conclusion, the mice with deficiency of GCGDPs developed peripheral neuropathy with age. Furthermore, glucagon might have neuroprotective effects on the PNS of mice. GCGDPs might be involved in the pathology of DPN.

Topics: Animals; Diabetic Neuropathies; Disease Models, Animal; Ganglia, Spinal; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Fibers, Myelinated; Neural Conduction; Neuronal Outgrowth; Receptors, Glucagon; RNA, Messenger

Topics: Antidepressive Agents; Demyelinating Diseases; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Nerve Degeneration; Neuralgia; Peptides; Research