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Activation of AMP-Activated Protein Kinase by Interleukin-6 in Rat Skeletal Muscle: Association With Changes in cAMP, Energy State, and Endogenous Fuel Mobilization

OBJECTIVE: Interleukin-6 (IL-6) directly activates AMP-activated protein kinase (AMPK) in vivo and in vitro; however, the mechanism by which it does so is unknown. RESEARCH DESIGN AND METHODS: We examined this question in skeletal muscle using an incubated rat extensor digitorum longus (EDL) muscle...

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Detalles Bibliográficos
Autores principales: Kelly, Meghan, Gauthier, Marie-Soleil, Saha, Asish K., Ruderman, Neil B.
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731526/
https://www.ncbi.nlm.nih.gov/pubmed/19502419
http://dx.doi.org/10.2337/db08-1293
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author Kelly, Meghan
Gauthier, Marie-Soleil
Saha, Asish K.
Ruderman, Neil B.
author_facet Kelly, Meghan
Gauthier, Marie-Soleil
Saha, Asish K.
Ruderman, Neil B.
author_sort Kelly, Meghan
collection PubMed
description OBJECTIVE: Interleukin-6 (IL-6) directly activates AMP-activated protein kinase (AMPK) in vivo and in vitro; however, the mechanism by which it does so is unknown. RESEARCH DESIGN AND METHODS: We examined this question in skeletal muscle using an incubated rat extensor digitorum longus (EDL) muscle preparation as a tool. RESULTS: AMPK activation by IL-6 coincided temporally with a nearly threefold increase in the AMP:ATP ratio in the EDL. The effects of IL-6 on both AMPK activity and energy state were inhibited by coincubation with propranolol, suggesting involvement of β-adrenergic signaling. In keeping with this notion, IL-6 concurrently induced a transient increase in cAMP, and its ability to activate AMPK was blocked by the adenyl cyclase inhibitor 2′5′-dideoxyadenosine. In addition, like other β-adrenergic stimuli, IL-6 increased glycogen breakdown and lipolysis in the EDL. Similar effects of IL-6 on AMPK, energy state, and cAMP content were observed in C2C12 myotubes and gastrocnemius muscle in vivo, indicating that they were not unique to the incubated EDL. CONCLUSIONS: These studies demonstrate that IL-6 activates AMPK in skeletal muscle by increasing the concentration of cAMP and, secondarily, the AMP:ATP ratio. They also suggest that substantial increases in IL-6 concentrations, such as those that can result from its synthesis by muscles during exercise, may play a role in the mobilization of fuel stores within skeletal muscle as an added means of restoring energy balance.
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spelling pubmed-27315262010-09-01 Activation of AMP-Activated Protein Kinase by Interleukin-6 in Rat Skeletal Muscle: Association With Changes in cAMP, Energy State, and Endogenous Fuel Mobilization Kelly, Meghan Gauthier, Marie-Soleil Saha, Asish K. Ruderman, Neil B. Diabetes Original Article OBJECTIVE: Interleukin-6 (IL-6) directly activates AMP-activated protein kinase (AMPK) in vivo and in vitro; however, the mechanism by which it does so is unknown. RESEARCH DESIGN AND METHODS: We examined this question in skeletal muscle using an incubated rat extensor digitorum longus (EDL) muscle preparation as a tool. RESULTS: AMPK activation by IL-6 coincided temporally with a nearly threefold increase in the AMP:ATP ratio in the EDL. The effects of IL-6 on both AMPK activity and energy state were inhibited by coincubation with propranolol, suggesting involvement of β-adrenergic signaling. In keeping with this notion, IL-6 concurrently induced a transient increase in cAMP, and its ability to activate AMPK was blocked by the adenyl cyclase inhibitor 2′5′-dideoxyadenosine. In addition, like other β-adrenergic stimuli, IL-6 increased glycogen breakdown and lipolysis in the EDL. Similar effects of IL-6 on AMPK, energy state, and cAMP content were observed in C2C12 myotubes and gastrocnemius muscle in vivo, indicating that they were not unique to the incubated EDL. CONCLUSIONS: These studies demonstrate that IL-6 activates AMPK in skeletal muscle by increasing the concentration of cAMP and, secondarily, the AMP:ATP ratio. They also suggest that substantial increases in IL-6 concentrations, such as those that can result from its synthesis by muscles during exercise, may play a role in the mobilization of fuel stores within skeletal muscle as an added means of restoring energy balance. American Diabetes Association 2009-09 2009-06-05 /pmc/articles/PMC2731526/ /pubmed/19502419 http://dx.doi.org/10.2337/db08-1293 Text en © 2009 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Article
Kelly, Meghan
Gauthier, Marie-Soleil
Saha, Asish K.
Ruderman, Neil B.
Activation of AMP-Activated Protein Kinase by Interleukin-6 in Rat Skeletal Muscle: Association With Changes in cAMP, Energy State, and Endogenous Fuel Mobilization
title Activation of AMP-Activated Protein Kinase by Interleukin-6 in Rat Skeletal Muscle: Association With Changes in cAMP, Energy State, and Endogenous Fuel Mobilization
title_full Activation of AMP-Activated Protein Kinase by Interleukin-6 in Rat Skeletal Muscle: Association With Changes in cAMP, Energy State, and Endogenous Fuel Mobilization
title_fullStr Activation of AMP-Activated Protein Kinase by Interleukin-6 in Rat Skeletal Muscle: Association With Changes in cAMP, Energy State, and Endogenous Fuel Mobilization
title_full_unstemmed Activation of AMP-Activated Protein Kinase by Interleukin-6 in Rat Skeletal Muscle: Association With Changes in cAMP, Energy State, and Endogenous Fuel Mobilization
title_short Activation of AMP-Activated Protein Kinase by Interleukin-6 in Rat Skeletal Muscle: Association With Changes in cAMP, Energy State, and Endogenous Fuel Mobilization
title_sort activation of amp-activated protein kinase by interleukin-6 in rat skeletal muscle: association with changes in camp, energy state, and endogenous fuel mobilization
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731526/
https://www.ncbi.nlm.nih.gov/pubmed/19502419
http://dx.doi.org/10.2337/db08-1293
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