title: Endurance training improves responsiveness to insulin and modulates insulin signal transduction through the phosphatidylinositol 3-kinase/Akt-1 pathway.
abstract: BACKGROUND
  Endurance training increases insulin-stimulated muscle glucose transport and leads to improved metabolic control in diabetic patients.
  
  
  OBJECTIVE
  To analyze the effects of endurance training on the early steps of insulin action in muscle of rats.
  
  
  METHODS
  Male rats submitted to daily swimming for 6 weeks were compared with sedentary controls. At the end of the training period, anesthetized animals received an intravenous (i.v.) injection of insulin and had a fragment of their gastrocnemius muscle excised for the experiments.
  
  
  METHODS
  Associations between insulin receptor, insulin receptor substrates (IRS)-1 and -2 and phosphatidylinositol 3-kinase (PI3-kinase) were analyzed by immunoprecipitation and immunoblotting. Akt-1 serine phosphorylation and specific protein quantification were detected by immunoblotting of total extracts, and IRS-1/IRS-2-associated PI3-kinase activity were determined by thin-layer chromatography.
  
  
  RESULTS
  Insulin-induced phosphorylation of IRS-1 and IRS-2 increased respectively by 1.8-fold (P<0.05) and 1.5-fold (P<0.05), whereas their association with PI3-kinase increased by 2.3-fold (P<0.05) and 1.9-fold (P<0.05) in trained rats as compared with sedentary controls, respectively. The activity of PI3-kinase associated with IRS-1 and IRS-2 increased by 1.8-fold (P<0.05) and 1.7-fold (P<0.05) respectively, in trained rats as compared with their untrained counterparts. Serine phosphorylation of Akt-1/PKB increased 1.7-fold (P<0.05) in trained rats in response to insulin. These findings were accompanied by increased responsiveness to insulin as demonstrated by a reduced area under the curve for insulin during an i.v. glucose tolerance test, by increased glucose disappearance rate during an insulin tolerance test, and by increased expression of glucose transporter-4.
  
  
  CONCLUSIONS
  The increased responsiveness to insulin induced by chronic exercise in rat skeletal muscle may result, at least in part, from the modulation of the insulin signaling pathway at different molecular levels.
authors.affiliation: Department of Physical Education, State University of São Paulo (UNESP), Rio Claro, Brazil.
authors.forename: Eliete
authors.initials: E
authors.lastname: Luciano
authors.forename: Everardo M
authors.initials: EM
authors.lastname: Carneiro
authors.forename: Carla R O
authors.initials: CR
authors.lastname: Carvalho
authors.forename: José B C
authors.initials: JB
authors.lastname: Carvalheira
authors.forename: Sidney B
authors.initials: SB
authors.lastname: Peres
authors.forename: Marise A B
authors.initials: MA
authors.lastname: Reis
authors.forename: Mario J A
authors.initials: MJ
authors.lastname: Saad
authors.forename: A Carlos
authors.initials: AC
authors.lastname: Boschero
authors.forename: Licio A
authors.initials: LA
authors.lastname: Velloso
mesh_terms: D000818:Animals; D007004:Hypoglycemic Agents / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; C494920:Akt1 protein, rat