Interactions of exercise training and α-lipoic acid on insulin signaling in skeletal muscle of obese Zucker rats

Vitoon Saengsirisuwan, Felipe R. Perez, Julie A. Sloniger, Thomas Maier, Erik J. Henriksen

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


We have shown previously (Saengsirisuwan V, Kinnick TR, Schmit MB, and Henriksen EJ. J Appl Physiol 91: 145-153, 2001) that the antioxidant R-(+)-α-lipoic acid (R-ALA), combined with endurance exercise training (ET), increases glucose transport in insulin-resistant skeletal muscle in an additive fashion. The purpose of the present study was to investigate possible cellular mechanisms responsible for this interactive effect. We evaluated the effects of R-ALA alone, ET alone, or R-ALA and ET in combination on insulin-stimulated glucose transport, protein expression, and functionality of specific insulin-signaling factors in soleus muscle of obese Zucker (fa/fa) rats. Obese animals remained sedentary, received R-ALA (30 mg·kg body wt-1·day-1), performed ET (daily treadmill running for ≤60 min), or underwent both R-ALA treatment and ET for 15 days. R-ALA or ET individually increased (P < 0.05) insulin-mediated (5 mU/ml) glucose transport (2-deoxyglucose uptake) in soleus muscle by 45 and 68%, respectively, and this value was increased to the greatest extent (124%) in the combined treatment group. Soleus insulin receptor substrate (IRS)-1 protein was significantly increased by R-ALA alone (30%) or ET alone (31%), and a further enhancement (55%) was observed after the combination treatment in the obese animals. Enhanced levels of IRS-1 protein expression after individual or combined interventions were significantly correlated with insulin action on glucose transport activity (r = 0.597, P = 0.0055). Similarly, insulin-mediated IRS-1 associated with the p85 regulatory subunit of phosphatidylinositol 3-kinase was increased by R-ALA (317%) and ET (319%) and to the greatest extent (435%) (all P < 0.05) by the combination treatment. These results indicate that the improvements of insulin action in insulin-resistant skeletal muscle after R-ALA or ET, alone and in combination, were associated with increases in IRS-1 protein expression and IRS-1 associated with p85.

Original languageEnglish (US)
Pages (from-to)E529-E536
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number3 50-3
StatePublished - Sep 2004


  • Antioxidants
  • Glucose transport
  • Insulin receptor substrate-1
  • Insulin resistance
  • p85

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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