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Leal-Julià M, Vilches JJ, Onieva A, et al. PROTEOMIC QUANTITATIVE STUDY OF DORSAL ROOT GANGLIA AND SCIATIC NERVE IN TYPE 2 DIABETIC MICE. Mol Metab. 2021;101408doi: 10.1016/j.molmet.2021.101408.
Leal-Julià, M., Vilches, J. J., Onieva, A., Verdés, S., Sánchez, �. �., Chillón, M., Navarro, X., & Bosch, A. (2021). PROTEOMIC QUANTITATIVE STUDY OF DORSAL ROOT GANGLIA AND SCIATIC NERVE IN TYPE 2 DIABETIC MICE. Molecular metabolism, 101408. https://doi.org/10.1016/j.molmet.2021.101408
Leal-Julià, Marc, et al. "PROTEOMIC QUANTITATIVE STUDY OF DORSAL ROOT GANGLIA AND SCIATIC NERVE IN TYPE 2 DIABETIC MICE." Molecular metabolism vol. (2021): 101408. doi: https://doi.org/10.1016/j.molmet.2021.101408
Leal-Julià M, Vilches JJ, Onieva A, Verdés S, Sánchez Á, Chillón M, Navarro X, Bosch A. PROTEOMIC QUANTITATIVE STUDY OF DORSAL ROOT GANGLIA AND SCIATIC NERVE IN TYPE 2 DIABETIC MICE. Mol Metab. 2021 Nov 29;101408. doi: 10.1016/j.molmet.2021.101408. Epub 2021 Nov 29. PMID: 34856394.
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Mol Metab. 2021 Nov 29;101408. doi: 10.1016/j.molmet.2021.101408. Epub 2021 Nov 29.

PROTEOMIC QUANTITATIVE STUDY OF DORSAL ROOT GANGLIA AND SCIATIC NERVE IN TYPE 2 DIABETIC MICE.

Molecular metabolism

Marc Leal-Julià, Jorge J Vilches, Andrea Onieva, Sergi Verdés, Ángela Sánchez, Miguel Chillón, Xavier Navarro, Assumpció Bosch

Affiliations

  1. Institute of Neurosciences, Univ. Autònoma de Barcelona, Spain; Department of Biochemistry and Molecular Biology, Univ. Autònoma de Barcelona, Spain; Unitat Mixta UAB-VHIR, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
  2. Institute of Neurosciences, Univ. Autònoma de Barcelona, Spain; Department of Cell Biology, Physiology and Immunology, Univ. Autònoma de Barcelona, Spain.
  3. Institute of Neurosciences, Univ. Autònoma de Barcelona, Spain; Department of Biochemistry and Molecular Biology, Univ. Autònoma de Barcelona, Spain; Institut Català de Recerca i Estudis Avançats (ICREA), Barcelona, Spain; Unitat Mixta UAB-VHIR, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
  4. Institute of Neurosciences, Univ. Autònoma de Barcelona, Spain; Department of Cell Biology, Physiology and Immunology, Univ. Autònoma de Barcelona, Spain; Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Spain.
  5. Institute of Neurosciences, Univ. Autònoma de Barcelona, Spain; Department of Biochemistry and Molecular Biology, Univ. Autònoma de Barcelona, Spain; Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Spain; Unitat Mixta UAB-VHIR, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Electronic address: [email protected].

PMID: 34856394 DOI: 10.1016/j.molmet.2021.101408

Abstract

OBJECTIVE: Peripheral neuropathy is the most common and debilitating complication of type 2 diabetes leading to sensory loss, dysautonomia, hyperalgesia and spontaneous noxious sensations. Despite clinical and economic burden of diabetic neuropathy, no effective treatment is available. Thus, more preclinical research must be conducted to gain further understanding of the aetiology of the disease and elucidate new therapeutic targets.

METHODS: The proteome of lumbar dorsal root ganglia and sciatic nerve of BKS-db/db mice, which contain a mutation of the leptin receptor and are an established type 2 diabetes model, was characterized for the first time by tandem mass tag labelling and mass spectrometry analysis.

RESULTS: Proteomic analysis showed differentially expressed proteins grouped into functional clusters in db/db peripheral nerves compared to control mice, underlining reduced glycolytic and TCA cycle metabolism, higher lipid catabolism, upregulation of muscle-like proteins in DRG and downregulation in SCN, increased cytoskeleton-related proteins, a mild dysregulation of folding chaperones, activation of acute-phase and inflammatory response, and alterations in glutathione metabolism and oxidative stress related proteins.

CONCLUSIONS: Our data validate previous transcriptomic and metabolomic results as well as uncover new pathways altered in diabetic neuropathy. Importantly, our results point out that energetic deficiency could represent the main mechanism of neurodegeneration observed in diabetic neuropathy. These findings may provide important information to select appropriate targets to develop new therapeutic strategies.

Copyright © 2021. Published by Elsevier GmbH.

Keywords: Diabetes; Dorsal root ganglia; Neuropathy; Obesity; Proteomics; Sciatic nerve

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