Resistance exercise increases human skeletal muscle AS160/TBC1D4 phosphorylation in association with enhanced leg glucose uptake during postexercise recovery

Hans C. Dreyer, Micah J. Drummond, Erin L. Glynn, Satoshi Fujita, David L. Chinkes, Elena Volpi, Blake B. Rasmussen

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25 Scopus citations


Akt substrate of 160 kDa (AS160/TBC1D4) is associated with insulin and contraction-mediated glucose uptake. Human skeletal muscle AS160 phosphorylation is increased during aerobic exercise but not immediately following resistance exercise. It is not known whether AS160 phosphorylation is altered during recovery from resistance exercise. Therefore, we hypothesized that muscle AS160/TBC1D4 phosphorylation and glucose uptake across the leg would be increased during recovery following resistance exercise. We studied 9 male subjects before, during, and for 2 h of postexercise recovery. We utilized femoral catheterizations and muscle biopsies in combination with indirect calorimetry and immunoblotting to determine whole body glucose and fat oxidation, leg glucose uptake, muscle AMPKα2 activity, and the phosphorylation of muscle Akt and AS160/TBC1D4. Glucose oxidation was reduced while fat oxidation increased (∼35%) during postexercise recovery (P ≤ 0.05). Glucose uptake increased during exercise and postexercise recovery (P ≤ 0.05). Akt phosphorylation was increased at 1 h and AMPKα2 activity increased at 2 h postexercise (P ≤ 0.05). Phospho(Ser/Thr)-Akt substrate (PAS) phosphorylation (often used as a marker for AS160) was unchanged immediately postexercise and increased at 1 h (P ≤ 0.05) and 2 h postexercise (P = 0.07). The PAS antibody is not always specific for AS160/TBC1D4 and can detect proteins at a similar molecular weight. Therefore, we immunoprecipitated AS160/TBC1D4 and then blotted with the PAS antibody, which confirmed that PAS phosphorylation is occurring on AS160/TBC1D4. There was also a positive correlation between PAS phosphorylation and leg glucose uptake during recovery (P ≤ 0.05). We conclude that resistance exercise increases AS160/TBC1D4 phosphorylation in association with an increase in leg glucose uptake during postexercise recovery.

Original languageEnglish (US)
Pages (from-to)1967-1974
Number of pages8
JournalJournal of Applied Physiology
Issue number6
StatePublished - Dec 1 2008



  • AMP-activated protein kinase
  • Akt
  • Fat oxidation
  • GLUT4

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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