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Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/44022
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dc.creatorDawit Albieiro Pinheiro Gonçalvespt_BR
dc.creatorWilian de Assis Silveirapt_BR
dc.creatorLeandro Henrique Manfredipt_BR
dc.creatorFlávia Aparecida Graçapt_BR
dc.creatorAndrea Armanipt_BR
dc.creatorEnrico Bertaggiapt_BR
dc.creatorBrian O'Neillpt_BR
dc.creatorNatália Lautherbach Ennes da Silvapt_BR
dc.creatorJuliano Machadopt_BR
dc.creatorLeonardo Nogarapt_BR
dc.creatorMarcelo Gomes Pereirapt_BR
dc.creatorDiletta Arcidiaconopt_BR
dc.creatorStefano Realdonpt_BR
dc.creatorCarl Ronald Kahnpt_BR
dc.creatorMarco Sandript_BR
dc.creatorIsis Do Carmo Kettelhutpt_BR
dc.creatorLuiz Carlos Carvalho Navegantespt_BR
dc.date.accessioned2022-08-08T11:56:36Z-
dc.date.available2022-08-08T11:56:36Z-
dc.date.issued2019-04-
dc.citation.volume10pt_BR
dc.citation.issue2pt_BR
dc.citation.spage131pt_BR
dc.citation.epage146pt_BR
dc.identifier.doihttps://doi.org/10.1002/jcsm.12395pt_BR
dc.identifier.issn2190-6009pt_BR
dc.identifier.urihttp://hdl.handle.net/1843/44022-
dc.description.resumoBackground: Stimulation of β2 -adrenoceptors can promote muscle hypertrophy and fibre type shift, and it can counteract atrophy and weakness. The underlying mechanisms remain elusive. Methods: Fed wild type (WT), 2-day fasted WT, muscle-specific insulin (INS) receptor (IR) knockout (M-IR-/- ), and MKR mice were studied with regard to acute effects of the β2 -agonist formoterol (FOR) on protein metabolism and signalling events. MKR mice express a dominant negative IGF1 receptor, which blocks both INS/IGF1 signalling. All received one injection of FOR (300 μg kg-1 subcutaneously) or saline. Skeletal muscles and serum samples were analysed from 30 to 240 min. For the study of chronic effects of FOR on muscle plasticity and function as well as intracellular signalling pathways, fed WT and MKR mice were treated with formoterol (300 μg kg-1 day-1 ) for 30 days. Results: In fed and fasted mice, one injection of FOR inhibited autophagosome formation (LC3-II content, 65%, P ≤ 0.05) that was paralleled by an increase in serum INS levels (4-fold to 25-fold, P ≤ 0.05) and the phosphorylation of Akt (4.4-fold to 6.5-fold, P ≤ 0.05) and ERK1/2 (50% to two-fold, P ≤ 0.05). This led to the suppression (40-70%, P ≤ 0.05) of the master regulators of atrophy, FoxOs, and the mRNA levels of their target genes. FOR enhanced (41%, P ≤ 0.05) protein synthesis only in fed condition and stimulated (4.4-fold to 35-fold, P ≤ 0.05) the prosynthetic Akt/mTOR/p70S6K pathway in both fed and fasted states. FOR effects on Akt signalling during fasting were blunted in both M-IR-/- and MKR mice. Inhibition of proteolysis markers by FOR was prevented only in MKR mice. Blockade of PI3K/Akt axis and mTORC1, but not ERK1/2, in fasted mice also suppressed the acute FOR effects on proteolysis and autophagy. Chronic stimulation of β2 -adrenoceptors in fed WT mice increased body (11%, P ≤ 0.05) and muscle (15%, P ≤ 0.05) growth and downregulated atrophy-related genes (30-40%, P ≤ 0.05), but these effects were abolished in MKR mice. Increases in muscle force caused by FOR (WT, 24%, P ≤ 0.05) were only partially impaired in MKR mice (12%, P ≤ 0.05), and FOR-induced slow-to-fast fibre type shift was not blocked at all in these animals. In MKR mice, FOR also restored the lower levels of muscle SDH activity to basal WT values and caused a marked reduction (57%, P ≤ 0.05) in the number of centrally nucleated fibers. Conclusions: NS/IGF1 signalling is necessary for the anti-proteolytic and hypertrophic effects of in vivo β2 -adrenergic stimulation and appears to mediate FOR-induced enhancement of protein synthesis. INS/IGF1 signalling only partially contributes to gain in strength and does not mediate fibre type transition induced by FORpt_BR
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.description.sponsorshipFAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.description.sponsorshipOutra Agênciapt_BR
dc.format.mimetypepdfpt_BR
dc.languageengpt_BR
dc.publisherUniversidade Federal de Minas Geraispt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.departmentEEF - DEPARTAMENTO DE EDUCAÇÃO FÍSICApt_BR
dc.publisher.initialsUFMGpt_BR
dc.relation.ispartofJournal of Cachexia, Sarcopenia and Musclept_BR
dc.rightsAcesso Abertopt_BR
dc.subjectβ2-adrenoceptorpt_BR
dc.subjectInsulin/IGF1signallingpt_BR
dc.subjectProtein metabolismpt_BR
dc.subjectSkeletal muscle functionpt_BR
dc.subjectSkeletal muscle plasticitypt_BR
dc.subjectAu-tophagy-lysosomal systempt_BR
dc.subject.otherBetabloqueadores adrenérgicospt_BR
dc.subject.otherInsulinapt_BR
dc.subject.otherProteínas - Metabolismopt_BR
dc.subject.otherMúsculo esqueléticopt_BR
dc.subject.otherMúsculos - Hipertrofiapt_BR
dc.subject.otherMusculos - Atrofiapt_BR
dc.titleInsulin/IGF1 signalling mediates the effects of β2-adrenergic agonist on muscle proteostasis and growthpt_BR
dc.typeArtigo de Periódicopt_BR
dc.url.externahttps://onlinelibrary.wiley.com/doi/10.1002/jcsm.12395pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0003-2621-3330pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-6171-7940pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-4157-8613pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0001-9890-5104pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-6670-8031pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-7583-9228pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0001-8509-7558pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-9034-5357pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-9870-9469pt_BR
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