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Leucine and mTORc1 act independently to regulate 2-deoxyglucose uptake in L6 myotubes

Yin, Qiong; Brameld, John M.; Parr, Tim; Murton, Andrew J.

Authors

Qiong Yin

JOHN BRAMELD JOHN.BRAMELD@NOTTINGHAM.AC.UK
Professor of Nutritional Biochemstry

TIM PARR tim.parr@nottingham.ac.uk
Professor of Nutritional Biochemistry

Andrew J. Murton



Abstract

© 2020, The Author(s). Chronic mTORc1 hyperactivation via obesity-induced hyperleucinaemia has been implicated in the development of insulin resistance, yet the direct impact of leucine on insulin-stimulated glucose uptake in muscle cells remains unclear. To address this, differentiated L6 myotubes were subjected to various compounds designed to either inhibit mTORc1 activity (rapamycin), blunt leucine intracellular import (BCH), or activate mTORc1 signalling (3BDO), prior to the determination of the uptake of the glucose analogue, 2-deoxyglucose (2-DG), in response to 1mM insulin. In separate experiments, L6 myotubes were subject to various media concentrations of leucine (0–0.8mM) for 24h before 2-DG uptake in response to insulin was assessed. Both rapamycin and BCH blunted 2-DG uptake, irrespective of insulin administration, and this occurred in parallel with a decline in mTOR, 4E-BP1, and p70S6K phosphorylation status, but little effect on AKT phosphorylation. In contrast, reducing leucine media concentrations suppressed 2-DG uptake, both under insulin- and non-insulin-stimulated conditions, but did not alter the phosphorylation state of AKT-mTORc1 components examined. Unexpectedly, 3BDO failed to stimulate mTORc1 signalling, but, nonetheless, caused a significant increase in 2-DG uptake under non-insulin-stimulated conditions. Both leucine and mTORc1 influence glucose uptake in muscle cells independent of insulin administration, and this likely occurs via distinct but overlapping mechanisms.

Journal Article Type Article
Publication Date 2020-03
Journal Amino Acids
Print ISSN 0939-4451
Electronic ISSN 1438-2199
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 52
Pages 477–486
APA6 Citation Yin, Q., Brameld, J. M., Parr, T., & Murton, A. J. (2020). Leucine and mTORc1 act independently to regulate 2-deoxyglucose uptake in L6 myotubes. Amino Acids, 52, 477–486. https://doi.org/10.1007/s00726-020-02829-0
DOI https://doi.org/10.1007/s00726-020-02829-0
Keywords Insulin resistance, Obesity, Muscle, Glucose uptake, Leucine, Branched chain amino acids
Publisher URL https://link.springer.com/article/10.1007%2Fs00726-020-02829-0
Additional Information Received: 5 September 2019; Accepted: 8 February 2020; First Online: 27 February 2020; : ; : The authors declare that they have no conflict of interest.

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