Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials / drug effects
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Action Potentials / genetics
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Age Factors
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Animals
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Blood Glucose / metabolism
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Body Weight / drug effects
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Body Weight / genetics
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Diabetes Mellitus, Type 2 / complications
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Diabetes Mellitus, Type 2 / pathology
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Disease Models, Animal
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Electric Stimulation
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Humans
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Kv1.2 Potassium Channel / metabolism*
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Male
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Mice
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Mice, Mutant Strains
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Mutation / genetics
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Neural Conduction / physiology
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Peripheral Nerves / metabolism*
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Peripheral Nerves / physiopathology*
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Peripheral Nervous System Diseases / etiology
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Peripheral Nervous System Diseases / pathology*
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Potassium Channel Blockers / pharmacology
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Protein Subunits / metabolism
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Ranvier's Nodes / metabolism*
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Receptors, Leptin / genetics
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Sodium Channel Blockers / pharmacology
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Sodium Channels / metabolism
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Tetrodotoxin / pharmacology
Substances
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Blood Glucose
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Kv1.2 Potassium Channel
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Potassium Channel Blockers
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Protein Subunits
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Receptors, Leptin
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Sodium Channel Blockers
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Sodium Channels
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Tetrodotoxin