title: Excessive training impairs the insulin signal transduction in mice skeletal muscles.
abstract: The main aim of this investigation was to verify the effects of overtraining (OT) on the insulin and inflammatory signaling pathways in mice skeletal muscles. Rodents were divided into control (CT), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR) groups. Rotarod, incremental load, exhaustive, and grip force tests were used to evaluate performance. Thirty-six hours after the grip force test, the extensor digitorum longus (EDL) and soleus were extracted for subsequent protein analyses. The three OT protocols led to similar responses of all performance evaluation tests. The phosphorylation of insulin receptor beta (pIRβ; Tyr), protein kinase B (pAkt; Ser473), and the protein levels of plasma membrane glucose transporter-4 (GLUT4) were lower in the EDL and soleus after the OTR/down protocol and in the soleus after the OTR/up and OTR protocols. While the pIRβ was lower after the OTR/up and OTR protocols, the pAkt was higher after the OTR/up in the EDL. The phosphorylation of IκB kinase alpha and beta (pIKKα/β; Ser180/181), stress-activated protein kinases/Jun amino-terminal kinases (pSAPK-JNK; Thr183/Tyr185), factor nuclear kappa B (pNFκB p65; Ser536), and insulin receptor substrate 1 (pIRS1; Ser307) were higher after the OTR/down protocol, but were not altered after the two other OT protocols. In summary, these data suggest that OT may lead to skeletal muscle insulin signaling pathway impairment, regardless of the predominance of eccentric contractions, although the insulin signal pathway impairment induced in OTR/up and OTR appeared to be muscle fiber-type specific.
authors.affiliation: Postgraduate Program in Rehabilitation and Functional PerformanceRibeirão Preto Medical School, USP, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Pereira
authors.affiliation: Postgraduate Program in Rehabilitation and Functional PerformanceRibeirão Preto Medical School, USP, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Alisson L
authors.initials: AL
authors.lastname: da Rocha
authors.affiliation: Postgraduate Program in Rehabilitation and Functional PerformanceRibeirão Preto Medical School, USP, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Pinto
authors.affiliation: Sport Sciences CourseFaculty of Applied Sciences, State University of Campinas, Limeira, São Paulo, Brazil.
authors.forename: José R
authors.initials: JR
authors.lastname: Pauli
authors.affiliation: Sport Sciences CourseFaculty of Applied Sciences, State University of Campinas, Limeira, São Paulo, Brazil.
authors.forename: Leandro P
authors.initials: LP
authors.lastname: de Moura
authors.affiliation: Department of NutritionHarvard School of Public Health, Boston, Massachusetts, USA Department of Social and Administrative SciencesMCPHS University, Boston, Massachusetts, USA.
authors.forename: Rania A
authors.initials: RA
authors.lastname: Mekary
authors.affiliation: School of Physical Education and Sport of Ribeirão PretoUniversity of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Ellen C
authors.initials: EC
authors.lastname: de Freitas
authors.affiliation: Postgraduate Program in Rehabilitation and Functional PerformanceRibeirão Preto Medical School, USP, Ribeirão Preto, São Paulo, Brazil School of Physical Education and Sport of Ribeirão PretoUniversity of São Paulo, Ribeirão Preto, São Paulo, Brazil adelinosanchez@usp.br.
authors.forename: Adelino S R
authors.initials: AS
authors.lastname: da Silva
mesh_terms: D000818:Animals; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt
keywords: exercise; insulin signaling; mouse; plasma membrane glut4