Literature DB >> 33161019

Effect of 2-deoxyglucose-mediated inhibition of glycolysis on the regulation of mTOR signaling and protein synthesis before and after high-intensity muscle contraction.

Takeshi Suginohara1, Koki Wakabayashi1, Satoru Ato1, Riki Ogasawara2.   

Abstract

BACKGROUND: Glycolysis controls mTORC1 signaling and protein synthesis. In skeletal muscle, glucose metabolism increases with both exercise/contraction intensity and volume, and therefore, high-intensity muscle contraction (HiMC) such as resistance exercise facilitates glycolysis including glucose uptake and glycogen breakdown. However, it is unknown whether glycolysis regulates HiMC-induced mTORC1 activation and increase in protein synthesis.
METHODS: To determine whether glycolysis regulates basal and HiMC-induced mTORC1 signaling and protein synthesis, we employed 2-deoxyglucose (2-DG) to inhibit glycolysis and isometrically contracted the gastrocnemius muscle of Sprague Dawley rats using percutaneous electrical stimulation.
RESULTS: Inhibition of glycolysis by 2-DG inhibited basal phosphorylation of p70S6K and 4E-BP1 (downstream targets of mTORC1) and protein synthesis (all P < 0.05) independent of AMPK phosphorylation. AMPK phosphorylation was comparably increased after HiMC at 0 h post HiMC and returned to basal levels 6 h post HiMC in both vehicle- and 2-DG-treated groups. Glycolysis inhibition attenuated muscle contraction-induced phosphorylation of 4E-BP1 at 6 h post HiMC (P < 0.05) but not p70S6K phosphorylation and protein synthesis.
CONCLUSION: Although glycolysis is involved in basal but not HiMC-induced muscle protein synthesis, it regulates both basal and HiMC-induced mTORC1 signaling, and may play key roles in skeletal muscle adaptation to HiMC.
Copyright © 2020 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Exercise; Glucose; Glycolytic metabolism; Metabolomics

Year:  2020        PMID: 33161019     DOI: 10.1016/j.metabol.2020.154419

Source DB:  PubMed          Journal:  Metabolism        ISSN: 0026-0495            Impact factor:   8.694


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