Mammalian target of rapamycin complex 2 regulates muscle glucose uptake during exercise in mice

Research output: Contribution to journalJournal articlepeer-review

Standard

Mammalian target of rapamycin complex 2 regulates muscle glucose uptake during exercise in mice. / Kleinert, Maximilian; Parker, Benjamin L; Fritzen, Andreas Mæchel; Knudsen, Jonas Roland; Jensen, Thomas Elbenhardt; Kjøbsted, Rasmus; Sylow, Lykke; Ruegg, Markus A; James, David E; Richter, Erik A.

In: Journal of Physiology, Vol. 595, No. 14, 2017, p. 4845-4855.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Kleinert, M, Parker, BL, Fritzen, AM, Knudsen, JR, Jensen, TE, Kjøbsted, R, Sylow, L, Ruegg, MA, James, DE & Richter, EA 2017, 'Mammalian target of rapamycin complex 2 regulates muscle glucose uptake during exercise in mice', Journal of Physiology, vol. 595, no. 14, pp. 4845-4855. https://doi.org/10.1113/JP274203

APA

Kleinert, M., Parker, B. L., Fritzen, A. M., Knudsen, J. R., Jensen, T. E., Kjøbsted, R., Sylow, L., Ruegg, M. A., James, D. E., & Richter, E. A. (2017). Mammalian target of rapamycin complex 2 regulates muscle glucose uptake during exercise in mice. Journal of Physiology, 595(14), 4845-4855. https://doi.org/10.1113/JP274203

Vancouver

Kleinert M, Parker BL, Fritzen AM, Knudsen JR, Jensen TE, Kjøbsted R et al. Mammalian target of rapamycin complex 2 regulates muscle glucose uptake during exercise in mice. Journal of Physiology. 2017;595(14):4845-4855. https://doi.org/10.1113/JP274203

Author

Kleinert, Maximilian ; Parker, Benjamin L ; Fritzen, Andreas Mæchel ; Knudsen, Jonas Roland ; Jensen, Thomas Elbenhardt ; Kjøbsted, Rasmus ; Sylow, Lykke ; Ruegg, Markus A ; James, David E ; Richter, Erik A. / Mammalian target of rapamycin complex 2 regulates muscle glucose uptake during exercise in mice. In: Journal of Physiology. 2017 ; Vol. 595, No. 14. pp. 4845-4855.

Bibtex

@article{e6b38591c6fb43c09b6459ecd865aff2,
title = "Mammalian target of rapamycin complex 2 regulates muscle glucose uptake during exercise in mice",
abstract = "Exercise increases glucose uptake into insulin-resistant muscle. Thus, elucidating the exercise signalling network in muscle may uncover new therapeutic targets. mTORC2, a regulator of insulin-controlled glucose uptake, has been reported to interact with Rac1, which plays a role in exercise-induced glucose uptake in muscle. Therefore, we tested the hypothesis that mTORC2 activity is necessary for muscle glucose uptake during treadmill exercise. We used mice that specifically lack mTORC2 signalling in muscle, by deletion of the obligatory mTORC2 component, Rictor (Ric mKO). Running capacity and running-induced changes in blood glucose, plasma lactate and muscle glycogen levels were similar in Ric WT and Ric mKO mice. At rest, muscle glucose uptake was normal, but during running muscle glucose uptake was reduced by 40% in Ric mKO mice. Running increased muscle p-AMPK similarly in Ric WT and Ric mKO mice and GLUT4 and HKII protein expressions were also normal in Ric mKO muscle. The mTORC2 substrate, p-PKCα, and the mTORC2 activity readout, p-NDRG1, increased with running in Ric WT mice, but were not altered by running in Ric mKO muscle. Quantitative phosphoproteomics uncovered several additional potential exercise-dependent mTORC2 substrates, including contractile proteins, kinases, transcriptional regulators, actin cytoskeleton regulators and ion-transport proteins. Our study suggests that mTORC2 is a component of the exercise signalling network that regulates muscle glucose uptake and we provide a resource of new potential members of the mTORC2 signalling network. This article is protected by copyright. All rights reserved.",
keywords = "mTOR, Running, NDRG, Phosphoproteomics",
author = "Maximilian Kleinert and Parker, {Benjamin L} and Fritzen, {Andreas M{\ae}chel} and Knudsen, {Jonas Roland} and Jensen, {Thomas Elbenhardt} and Rasmus Kj{\o}bsted and Lykke Sylow and Ruegg, {Markus A} and James, {David E} and Richter, {Erik A.}",
note = "CURIS 2017 NEXS 158",
year = "2017",
doi = "10.1113/JP274203",
language = "English",
volume = "595",
pages = "4845--4855",
journal = "The Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "14",

}

RIS

TY - JOUR

T1 - Mammalian target of rapamycin complex 2 regulates muscle glucose uptake during exercise in mice

AU - Kleinert, Maximilian

AU - Parker, Benjamin L

AU - Fritzen, Andreas Mæchel

AU - Knudsen, Jonas Roland

AU - Jensen, Thomas Elbenhardt

AU - Kjøbsted, Rasmus

AU - Sylow, Lykke

AU - Ruegg, Markus A

AU - James, David E

AU - Richter, Erik A.

N1 - CURIS 2017 NEXS 158

PY - 2017

Y1 - 2017

N2 - Exercise increases glucose uptake into insulin-resistant muscle. Thus, elucidating the exercise signalling network in muscle may uncover new therapeutic targets. mTORC2, a regulator of insulin-controlled glucose uptake, has been reported to interact with Rac1, which plays a role in exercise-induced glucose uptake in muscle. Therefore, we tested the hypothesis that mTORC2 activity is necessary for muscle glucose uptake during treadmill exercise. We used mice that specifically lack mTORC2 signalling in muscle, by deletion of the obligatory mTORC2 component, Rictor (Ric mKO). Running capacity and running-induced changes in blood glucose, plasma lactate and muscle glycogen levels were similar in Ric WT and Ric mKO mice. At rest, muscle glucose uptake was normal, but during running muscle glucose uptake was reduced by 40% in Ric mKO mice. Running increased muscle p-AMPK similarly in Ric WT and Ric mKO mice and GLUT4 and HKII protein expressions were also normal in Ric mKO muscle. The mTORC2 substrate, p-PKCα, and the mTORC2 activity readout, p-NDRG1, increased with running in Ric WT mice, but were not altered by running in Ric mKO muscle. Quantitative phosphoproteomics uncovered several additional potential exercise-dependent mTORC2 substrates, including contractile proteins, kinases, transcriptional regulators, actin cytoskeleton regulators and ion-transport proteins. Our study suggests that mTORC2 is a component of the exercise signalling network that regulates muscle glucose uptake and we provide a resource of new potential members of the mTORC2 signalling network. This article is protected by copyright. All rights reserved.

AB - Exercise increases glucose uptake into insulin-resistant muscle. Thus, elucidating the exercise signalling network in muscle may uncover new therapeutic targets. mTORC2, a regulator of insulin-controlled glucose uptake, has been reported to interact with Rac1, which plays a role in exercise-induced glucose uptake in muscle. Therefore, we tested the hypothesis that mTORC2 activity is necessary for muscle glucose uptake during treadmill exercise. We used mice that specifically lack mTORC2 signalling in muscle, by deletion of the obligatory mTORC2 component, Rictor (Ric mKO). Running capacity and running-induced changes in blood glucose, plasma lactate and muscle glycogen levels were similar in Ric WT and Ric mKO mice. At rest, muscle glucose uptake was normal, but during running muscle glucose uptake was reduced by 40% in Ric mKO mice. Running increased muscle p-AMPK similarly in Ric WT and Ric mKO mice and GLUT4 and HKII protein expressions were also normal in Ric mKO muscle. The mTORC2 substrate, p-PKCα, and the mTORC2 activity readout, p-NDRG1, increased with running in Ric WT mice, but were not altered by running in Ric mKO muscle. Quantitative phosphoproteomics uncovered several additional potential exercise-dependent mTORC2 substrates, including contractile proteins, kinases, transcriptional regulators, actin cytoskeleton regulators and ion-transport proteins. Our study suggests that mTORC2 is a component of the exercise signalling network that regulates muscle glucose uptake and we provide a resource of new potential members of the mTORC2 signalling network. This article is protected by copyright. All rights reserved.

KW - mTOR

KW - Running

KW - NDRG

KW - Phosphoproteomics

U2 - 10.1113/JP274203

DO - 10.1113/JP274203

M3 - Journal article

C2 - 28464351

VL - 595

SP - 4845

EP - 4855

JO - The Journal of Physiology

JF - The Journal of Physiology

SN - 0022-3751

IS - 14

ER -

ID: 178257401