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Altered distribution of juxtaparanodal kv1.2 subunits mediates peripheral nerve hyperexcitability in type 2 diabetes mellitus.
Journal of Neuroscience
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Peripheral nerve hyperexcitability (PNH) is one of the distal peripheral neuropathy phenotypes often present in patients affected by type 2 diabetes mellitus (T2DM). Through in vivo and ex vivo electrophysiological recordings in db/db mice, a model of T2DM, we observed that, in addition to reduced nerve conduction velocity, db/db mice also develop PNH. By using pharmacological inhibitors, we demonstrated that the PNH is mediated by the decreased activity of K(v)1-channels. In agreement with these data, we observed that the diabetic condition led to a reduced presence of the K(v)1.2-subunits in juxtaparanodal regions of peripheral nerves in db/db mice and in nerve biopsies from T2DM patients. Together, these observations indicate that the T2DM condition leads to potassium channel-mediated PNH, thus identifying them as a potential drug target to treat some of the DPN related symptoms.
Action Potentials/drug effects, Action Potentials/genetics, Age Factors, Animals, Blood Glucose/metabolism, Body Weight/drug effects, Body Weight/genetics, Diabetes Mellitus, Type 2/complications, Diabetes Mellitus, Type 2/pathology, Disease Models, Animal, Electric Stimulation, Humans, Kv1.2 Potassium Channel/metabolism, Male, Mice, Mice, Mutant Strains, Mutation/genetics, Neural Conduction/physiology, Peripheral Nerves/metabolism, Peripheral Nerves/physiopathology, Peripheral Nervous System Diseases/etiology, Peripheral Nervous System Diseases/pathology, Potassium Channel Blockers/pharmacology, Protein Subunits/metabolism, Ranvier's Nodes/metabolism, Receptors, Leptin/genetics, Sodium Channel Blockers/pharmacology, Sodium Channels/metabolism, Tetrodotoxin/pharmacology
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