title: Altered regulation of contraction-induced Akt/mTOR/p70S6k pathway signaling in skeletal muscle of the obese Zucker rat.
abstract: Increased muscle loading results in the phosphorylation of the 70 kDa ribosomal S6 kinase (p70S6k), and this event is strongly correlated with the degree of muscle adaptation following resistance exercise. Whether insulin resistance or the comorbidities associated with this disorder may affect the ability of skeletal muscle to activate p70S6k signaling following an exercise stimulus remains unclear. Here, we compare the contraction-induced activation of p70S6k signaling in the plantaris muscles of lean and insulin resistant obese Zucker rats following a single bout of increased contractile loading. Compared to lean animals, the basal phosphorylation of p70S6k (Thr389; 37.2% and Thr421/Ser424; 101.4%), Akt (Thr308; 25.1%), and mTOR (Ser2448; 63.0%) was higher in obese animals. Contraction increased the phosphorylation of p70S6k (Thr389), Akt (Ser473), and mTOR (Ser2448) in both models however the magnitude and kinetics of activation differed between models. These results suggest that contraction-induced activation of p70S6k signaling is altered in the muscle of the insulin resistant obese Zucker rat.
authors.affiliation: Department of Pharmacology, Joan C Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA.
authors.forename: Anjaiah
authors.initials: A
authors.lastname: Katta
authors.forename: Sunil
authors.initials: S
authors.lastname: Kakarla
authors.forename: Miaozong
authors.initials: M
authors.lastname: Wu
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Paturi
authors.forename: Murali K
authors.initials: MK
authors.lastname: Gadde
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Arvapalli
authors.forename: Madhukar
authors.initials: M
authors.lastname: Kolli
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Rice
authors.forename: Eric R
authors.initials: ER
authors.lastname: Blough
mesh_terms: D000818:Animals; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D018149:Glucose Intolerance / Q000378:metabolism / Q000503:physiopathology; D006946:Hyperinsulinism / Q000378:metabolism / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000201:enzymology; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C546845:mTOR protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases