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Inorganic nitrate mimics exercise-stimulated muscular fiber-type switching and myokine and GABA release

Inorganic nitrate mimics exercise-stimulated muscular fiber-type switching and myokine and GABA release
Inorganic nitrate mimics exercise-stimulated muscular fiber-type switching and myokine and GABA release
Exercise is an effective intervention for prevention and treatment of type 2 diabetes. Skeletal muscle combines multiple signals contributing to the beneficial effects of exercise on cardiometabolic health. Inorganic nitrate increases exercise efficiency, tolerance and performance. The transcriptional regulator peroxisome proliferator-activated receptor? coactivator1? (PGC1?) coordinates the exercise-stimulated skeletal muscle fiber-type switch from glycolytic fast-twitch (type IIb) to oxidative slow-twitch (type I) and intermediate (type IIa) fibers; an effect reversed in insulin resistance and diabetes. We find that nitrate induces PGC1? expression and a switch towards type I and IIa fibers in rat muscle and myotubes in vitro. Nitrate induces the release of exercise/PGC1?-dependent myokine FNDC5/irisin, and ?-aminoisobutyric acid from myotubes, and muscle in rats and humans. Both exercise and nitrate stimulated, PGC1?-mediated, ?-aminobutyric acid (GABA) secretion from muscle. Circulating GABA concentrations were increased in exercising mice and nitrate-treated rats and humans, thus, GABA may function as an exercise/PGC1?-mediated myokine-like small molecule. Moreover, nitrate increased circulating growth hormone levels in humans and rodents. Nitrate induces physiological responses that mimic exercise training and may underlie the beneficial effects of this metabolite on exercise and cardiometabolic health.
0012-1797
1-42
Roberts, Lee
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Ashmore, Tom
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McNally, Ben
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Murfitt, Steven
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Fernandez, Bernadette
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Feelisch, Martin
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Lindsay, Ross
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Siervo, Mario
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Williams, Elizabeth
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Murray, Andrew
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Griffin, Julian
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Roberts, Lee
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Ashmore, Tom
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McNally, Ben
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Murfitt, Steven
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Fernandez, Bernadette
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Feelisch, Martin
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Lindsay, Ross
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Siervo, Mario
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Williams, Elizabeth
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Murray, Andrew
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Griffin, Julian
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Roberts, Lee, Ashmore, Tom, McNally, Ben, Murfitt, Steven, Fernandez, Bernadette, Feelisch, Martin, Lindsay, Ross, Siervo, Mario, Williams, Elizabeth, Murray, Andrew and Griffin, Julian (2016) Inorganic nitrate mimics exercise-stimulated muscular fiber-type switching and myokine and GABA release. Diabetes, 1-42. (doi:10.2337/db16-0843). (PMID:28028076)

Record type: Article

Abstract

Exercise is an effective intervention for prevention and treatment of type 2 diabetes. Skeletal muscle combines multiple signals contributing to the beneficial effects of exercise on cardiometabolic health. Inorganic nitrate increases exercise efficiency, tolerance and performance. The transcriptional regulator peroxisome proliferator-activated receptor? coactivator1? (PGC1?) coordinates the exercise-stimulated skeletal muscle fiber-type switch from glycolytic fast-twitch (type IIb) to oxidative slow-twitch (type I) and intermediate (type IIa) fibers; an effect reversed in insulin resistance and diabetes. We find that nitrate induces PGC1? expression and a switch towards type I and IIa fibers in rat muscle and myotubes in vitro. Nitrate induces the release of exercise/PGC1?-dependent myokine FNDC5/irisin, and ?-aminoisobutyric acid from myotubes, and muscle in rats and humans. Both exercise and nitrate stimulated, PGC1?-mediated, ?-aminobutyric acid (GABA) secretion from muscle. Circulating GABA concentrations were increased in exercising mice and nitrate-treated rats and humans, thus, GABA may function as an exercise/PGC1?-mediated myokine-like small molecule. Moreover, nitrate increased circulating growth hormone levels in humans and rodents. Nitrate induces physiological responses that mimic exercise training and may underlie the beneficial effects of this metabolite on exercise and cardiometabolic health.

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Accepted/In Press date: 18 December 2016
e-pub ahead of print date: 27 December 2016
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 405125
URI: https://eprints.soton.ac.uk/id/eprint/405125
ISSN: 0012-1797
PURE UUID: dcff20a7-1c2a-47f8-821a-c6ca859af6d8
ORCID for Bernadette Fernandez: ORCID iD orcid.org/0000-0001-6337-0381
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 27 Jan 2017 11:34
Last modified: 10 Dec 2019 01:37

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Contributors

Author: Lee Roberts
Author: Tom Ashmore
Author: Ben McNally
Author: Steven Murfitt
Author: Bernadette Fernandez ORCID iD
Author: Martin Feelisch ORCID iD
Author: Ross Lindsay
Author: Mario Siervo
Author: Elizabeth Williams
Author: Andrew Murray
Author: Julian Griffin

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