Reducing monocarboxylate transporter MCT1 worsens experimental diabetic peripheral neuropathy.
Animals
Axons
/ pathology
Behavior, Animal
Demyelinating Diseases
/ pathology
Diabetes Mellitus, Experimental
/ pathology
Diabetic Neuropathies
/ pathology
Ganglia, Spinal
/ metabolism
Hypesthesia
/ genetics
Lactic Acid
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Monocarboxylic Acid Transporters
/ genetics
Neural Conduction
/ drug effects
Sciatic Nerve
/ metabolism
Symporters
/ genetics
Diabetic peripheral neuropathy
Dorsal root ganglion
Metabolism
Monocarboxylate transporter
Peripheral nerve
Journal
Experimental neurology
ISSN: 1090-2430
Titre abrégé: Exp Neurol
Pays: United States
ID NLM: 0370712
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
20
07
2020
accepted:
21
07
2020
pubmed:
28
7
2020
medline:
6
3
2021
entrez:
28
7
2020
Statut:
ppublish
Résumé
Diabetic peripheral neuropathy (DPN) is one of the most common complications in diabetic patients. Though the exact mechanism for DPN is unknown, it clearly involves metabolic dysfunction and energy failure in multiple cells within the peripheral nervous system. Lactate is an alternate source of metabolic energy that is increasingly recognized for its role in supporting neurons. The primary transporter for lactate in the nervous system, monocarboxylate transporter-1 (MCT1), has been shown to be critical for peripheral nerve regeneration and metabolic support to neurons/axons. In this study, MCT1 was reduced in both sciatic nerve and dorsal root ganglia in wild-type mice treated with streptozotocin (STZ), a common model of type-1 diabetes. Heterozygous MCT1 null mice that developed hyperglycemia following STZ treatment developed a more severe DPN compared to wild-type mice, as measured by greater axonal demyelination, decreased peripheral nerve function, and increased numbness to innocuous low-threshold mechanical stimulation. Given that MCT1 inhibitors are being developed as both immunosuppressive and chemotherapeutic medications, our results suggest that clinical development in patients with diabetes should proceed with caution. Collectively, our findings uncover an important role for MCT1 in DPN and provide a potential lead toward developing novel treatments for this currently untreatable disease.
Identifiants
pubmed: 32717355
pii: S0014-4886(20)30246-6
doi: 10.1016/j.expneurol.2020.113415
pmc: PMC7502508
mid: NIHMS1616955
pii:
doi:
Substances chimiques
Monocarboxylic Acid Transporters
0
Symporters
0
monocarboxylate transport protein 1
0
Lactic Acid
33X04XA5AT
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
113415Subventions
Organisme : NINDS NIH HHS
ID : R01 NS086818
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS099320
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no competing financial interests.
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