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Urocortin 3 activates AMPK and AKT pathways and enhances glucose disposal in rat skeletal muscle

Insulin resistance (IR) in skeletal muscle is an important component of both type 2 diabetes and the syndrome of sarcopaenic obesity, for which there are no effective therapies. Urocortins (UCNs) are not only well established as neuropeptides but also have their roles in metabolism in peripheral tis...

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Autores principales: Roustit, Manon M, Vaughan, Joan M, Jamieson, Pauline M, Cleasby, Mark E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191181/
https://www.ncbi.nlm.nih.gov/pubmed/25122003
http://dx.doi.org/10.1530/JOE-14-0181
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author Roustit, Manon M
Vaughan, Joan M
Jamieson, Pauline M
Cleasby, Mark E
author_facet Roustit, Manon M
Vaughan, Joan M
Jamieson, Pauline M
Cleasby, Mark E
author_sort Roustit, Manon M
collection PubMed
description Insulin resistance (IR) in skeletal muscle is an important component of both type 2 diabetes and the syndrome of sarcopaenic obesity, for which there are no effective therapies. Urocortins (UCNs) are not only well established as neuropeptides but also have their roles in metabolism in peripheral tissues. We have shown recently that global overexpression of UCN3 resulted in muscular hypertrophy and resistance to the adverse metabolic effects of a high-fat diet. Herein, we aimed to establish whether short-term local UCN3 expression could enhance glucose disposal and insulin signalling in skeletal muscle. UCN3 was found to be expressed in right tibialis cranialis and extensor digitorum longus muscles of rats by in vivo electrotransfer and the effects studied vs the contralateral muscles after 1 week. No increase in muscle mass was detected, but test muscles showed 19% larger muscle fibre diameter (P=0.030), associated with increased IGF1 and IGF1 receptor mRNA and increased SER256 phosphorylation of forkhead transcription factor. Glucose clearance into the test muscles after an intraperitoneal glucose load was increased by 23% (P=0.018) per unit mass, associated with increased GLUT1 (34% increase; P=0.026) and GLUT4 (48% increase; P=0.0009) proteins, and significantly increased phosphorylation of insulin receptor substrate-1, AKT, AKT substrate of 160 kDa, glycogen synthase kinase-3β, AMP-activated protein kinase and its substrate acetyl coA carboxylase. Thus, UCN3 expression enhances glucose disposal and signalling in muscle by an autocrine/paracrine mechanism that is separate from its pro-hypertrophic effects, implying that such a manipulation may have promised for the treatment of IR syndromes including sarcopaenic obesity.
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spelling pubmed-41911812014-11-01 Urocortin 3 activates AMPK and AKT pathways and enhances glucose disposal in rat skeletal muscle Roustit, Manon M Vaughan, Joan M Jamieson, Pauline M Cleasby, Mark E J Endocrinol Research Insulin resistance (IR) in skeletal muscle is an important component of both type 2 diabetes and the syndrome of sarcopaenic obesity, for which there are no effective therapies. Urocortins (UCNs) are not only well established as neuropeptides but also have their roles in metabolism in peripheral tissues. We have shown recently that global overexpression of UCN3 resulted in muscular hypertrophy and resistance to the adverse metabolic effects of a high-fat diet. Herein, we aimed to establish whether short-term local UCN3 expression could enhance glucose disposal and insulin signalling in skeletal muscle. UCN3 was found to be expressed in right tibialis cranialis and extensor digitorum longus muscles of rats by in vivo electrotransfer and the effects studied vs the contralateral muscles after 1 week. No increase in muscle mass was detected, but test muscles showed 19% larger muscle fibre diameter (P=0.030), associated with increased IGF1 and IGF1 receptor mRNA and increased SER256 phosphorylation of forkhead transcription factor. Glucose clearance into the test muscles after an intraperitoneal glucose load was increased by 23% (P=0.018) per unit mass, associated with increased GLUT1 (34% increase; P=0.026) and GLUT4 (48% increase; P=0.0009) proteins, and significantly increased phosphorylation of insulin receptor substrate-1, AKT, AKT substrate of 160 kDa, glycogen synthase kinase-3β, AMP-activated protein kinase and its substrate acetyl coA carboxylase. Thus, UCN3 expression enhances glucose disposal and signalling in muscle by an autocrine/paracrine mechanism that is separate from its pro-hypertrophic effects, implying that such a manipulation may have promised for the treatment of IR syndromes including sarcopaenic obesity. Bioscientifica Ltd 2014-11 /pmc/articles/PMC4191181/ /pubmed/25122003 http://dx.doi.org/10.1530/JOE-14-0181 Text en © 2014 The authors http://creativecommons.org/licenses/by/3.0/deed.en_GB This work is licensed under a Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/deed.en_GB)
spellingShingle Research
Roustit, Manon M
Vaughan, Joan M
Jamieson, Pauline M
Cleasby, Mark E
Urocortin 3 activates AMPK and AKT pathways and enhances glucose disposal in rat skeletal muscle
title Urocortin 3 activates AMPK and AKT pathways and enhances glucose disposal in rat skeletal muscle
title_full Urocortin 3 activates AMPK and AKT pathways and enhances glucose disposal in rat skeletal muscle
title_fullStr Urocortin 3 activates AMPK and AKT pathways and enhances glucose disposal in rat skeletal muscle
title_full_unstemmed Urocortin 3 activates AMPK and AKT pathways and enhances glucose disposal in rat skeletal muscle
title_short Urocortin 3 activates AMPK and AKT pathways and enhances glucose disposal in rat skeletal muscle
title_sort urocortin 3 activates ampk and akt pathways and enhances glucose disposal in rat skeletal muscle
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191181/
https://www.ncbi.nlm.nih.gov/pubmed/25122003
http://dx.doi.org/10.1530/JOE-14-0181
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