Reducing monocarboxylate transporter MCT1 worsens experimental diabetic peripheral neuropathy.

Autor: Jha MK; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States., Ament XH; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States., Yang F; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States., Liu Y; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States., Polydefkis MJ; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States., Pellerin L; Inserm U1082, Universite de Poitiers, Poitiers Cedex 86021, France; Centre de Résonance Magnétique des Systèmes Biologiques, UMR5536 CNRS, LabEx TRAIL-IBIO, Université de Bordeaux, Bordeaux Cedex 33760, France., Morrison BM; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States. Electronic address: bmorris7@jhmi.edu.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2020 Nov; Vol. 333, pp. 113415. Date of Electronic Publication: 2020 Jul 25.
DOI: 10.1016/j.expneurol.2020.113415
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare no competing financial interests.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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