title: Impaired muscle AMPK activation in the metabolic syndrome may attenuate improved insulin action after exercise training.
abstract: BACKGROUND
  Strength training induces muscle remodeling and may improve insulin responsiveness.
  
  
  OBJECTIVE
  This study will quantify the impact of resistance training on insulin sensitivity in subjects with the metabolic syndrome and correlate this with activation of intramuscular pathways mediating mitochondrial biogenesis and muscle fiber hypertrophy.
  
  
  METHODS
  Ten subjects with the metabolic syndrome (MS) and nine sedentary controls underwent 8 wk of supervised resistance exercise training with pre- and posttraining anthropometric and muscle biochemical assessments.
  
  
  METHODS
  Resistance exercise training took place in a sports laboratory on a college campus.
  
  
  METHODS
  Pre- and posttraining insulin responsiveness was quantified using a euglycemic clamp. Changes in expression of muscle 5-AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathways were quantified using immunoblots.
  
  
  RESULTS
  Strength and stamina increased in both groups. Insulin sensitivity increased in controls (steady-state glucose infusion rate = 7.0 ± 2.0 mg/kg · min pretraining training vs. 8.7 ± 3.1 mg/kg · min posttraining; P < 0.01) but did not improve in MS subjects (3.3 ± 1.3 pre vs. 3.1 ± 1.0 post). Muscle glucose transporter 4 increased 67% in controls and 36% in the MS subjects. Control subjects increased muscle phospho-AMPK (43%), peroxisome proliferator-activated receptor γ coactivator 1α (57%), and ATP synthase (60%), more than MS subjects (8, 28, and 21%, respectively). In contrast, muscle phospho-mTOR increased most in the MS group (57 vs. 32%).
  
  
  CONCLUSIONS
  Failure of resistance training to improve insulin responsiveness in MS subjects was coincident with diminished phosphorylation of muscle AMPK, but increased phosphorylation of mTOR, suggesting activation of the mTOR pathway could be involved in inhibition of exercise training-related increases in AMPK and its activation and downstream events.
authors.affiliation: Center of Excellence for Sport Science and Coach Education, Department of Kinesiology, Leisure, and Sports Science, Clemmer College of Education, East Tennessee State University, Johnson City, Tennessee 37614, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Layne
authors.forename: Sami
authors.initials: S
authors.lastname: Nasrallah
authors.forename: Mark A
authors.initials: MA
authors.lastname: South
authors.forename: Mary E A
authors.initials: ME
authors.lastname: Howell
authors.forename: Melanie P
authors.initials: MP
authors.lastname: McCurry
authors.forename: Michael W
authors.initials: MW
authors.lastname: Ramsey
authors.forename: Michael H
authors.initials: MH
authors.lastname: Stone
authors.forename: Charles A
authors.initials: CA
authors.lastname: Stuart
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000328:Adult; D000704:Analysis of Variance; D015444:Exercise / Q000502:physiology*; D005260:Female; D015309:Glucose Clamp Technique; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D051296:Glucose Transporter Type 5 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D057185:Sedentary Behavior; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D051275:Glucose Transporter Type 4; D051296:Glucose Transporter Type 5; D007328:Insulin; C495692:SLC2A4 protein, human; C495726:SLC2A5 protein, human; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase