Partial dissociation of TSC2 and mTOR phosphorylation in cardiac and skeletal muscle of rats in vivo.
Insulin promotes protein accretion in cardiac and skeletal muscles through a stimulation of the mRNA translation initiation phase of protein synthesis. The present set of experiments examined the regulatory TSC2 signaling pathway that potentially contributes to the myocardial responsiveness of protein synthesis to insulin in post-absorptive male Sprague-Dawley rats in vivo. Heart and skeletal muscles were sampled from rats up to 1 h following intravenous injection of various doses of insulin. In cardiac muscle, TSC2 phosphorylation was elevated only at the highest plasma insulin concentration (386 ng/ml). In contrast, the extent of mTOR phosphorylation either on Ser((2448)) or Ser((2481)) was raised at 24-fold less concentration of insulin and corresponded with increased phosphorylation of PKB(Thr(308)) or PKB(Ser(473)). In gastrocnemius, TSC2 phosphorylation was elevated at plasma insulin concentrations (16 ng/ml) lower than that observed in cardiac muscle (386 ng insulin/ml). The increased TSC2 phosphorylation corresponded with a marked stimulation of PKB phosphorylation. However, mTOR(Ser(2448)) or mTOR(Ser(2481)) phosphorylation was not elevated until the plasma insulin concentration reached 97 ng/ml. The results indicate there is a dissociation of TSC2 and mTOR phosphorylation in vivo.
Forsyth
Sara
S
Department of Cellular and Molecular Physiology, Penn State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Vary
Thomas C
TC
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D007328:Insulin / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D007004:Hypoglycemic Agents; D007328:Insulin; C000624655:Tsc2 protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; D064413:3-Phosphoinositide-Dependent Protein Kinases; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases