title: Exercise training increases components of the c-Cbl-associated protein/c-Cbl signaling cascade in muscle of obese Zucker rats.
abstract: The purpose of this investigation was to determine whether alterations in the c-Cbl-associated protein/c-Cbl pathway and/or p38-mitogen-activated protein kinase (p38 MAP kinase) were associated with improved skeletal muscle insulin responsiveness in exercise-trained obese Zucker rats. Obese Zucker rats ran 5 d/wk on a motorized treadmill for 90 minutes over a 7-week period. Age-matched obese Zucker rats (OB-SED) and their lean littermates (LN-SED) were obtained to serve as nontrained controls. Twenty-four (OB-EX-24 h) or 48 hours (OB-EX-48 h) after the last exercise bout, the trained rats were studied via the hind limb perfusion technique in the presence of insulin. Insulin-stimulated glucose uptake was significantly decreased across the skeletal muscle of OB-SED rats compared with LN-SED, but was normalized in the obese rats by 7 weeks of training. The insulin-stimulated plasma membrane protein concentrations of TC10 and glucose transporter 4 were reduced in the sedentary Zuckers, but both proteins were increased by the training protocol. Training did not increase insulin-stimulated p38 MAP kinase protein concentration, nor did it have an effect on insulin-stimulated p38 MAP kinase phosphorylation at the plasma membrane. These results suggest that skeletal muscle insulin resistance is associated with reduced expression of TC10 and that this deficiency can be corrected with exercise training.
authors.affiliation: Exercise Physiology and Metabolism Laboratory, Department of Kinesiology and Health Education, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Bernard
authors.forename: Misato
authors.initials: M
authors.lastname: Saito
authors.forename: Yi-Hung
authors.initials: YH
authors.lastname: Liao
authors.forename: Ben B
authors.initials: BB
authors.lastname: Yaspelkis
authors.forename: John L
authors.initials: JL
authors.lastname: Ivy
mesh_terms: D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000032:analysis; D008840:Microfilament Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D050721:Proto-Oncogene Proteins c-cbl / Q000502:physiology*; D051381:Rats; D011924:Rats, Zucker; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis / Q000378:metabolism
chemical_list: D051275:Glucose Transporter Type 4; D008840:Microfilament Proteins; C495694:Slc2a4 protein, rat; C119201:ponsin; D050721:Proto-Oncogene Proteins c-cbl; D002950:Citrate (si)-Synthase; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose