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Am J Physiol Endocrinol Metab (April 6, 2004). doi:10.1152/ajpendo.00013.2004
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Submitted on January 9, 2004
Accepted on March 29, 2004

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

Vitoon Saengsirisuwan1, Felipe R. Perez1, Julie A. Sloniger1, Thomas Maier1, and Erik J. Henriksen1*

1 Muscle Metabolism Laboratory, Department of Physiology, University of Arizona, College of Medicine, Tucson, AZ, USA

* To whom correspondence should be addressed. E-mail: ejhenrik{at}u.arizona.edu.

We have shown previously (Saengsirisuwan et al., J. Appl. Physiol. 91: 145-153, 2001) that the antioxidant R-(+)-{alpha}-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 either remained sedentary, received R-ALA (30 mg/kg body wt/day), performed ET (daily treadmill running for up to 60 min), or underwent both RALA 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 IRS-1 protein was significantly increased by R-ALA alone (30%) or ET alone (31%), and a further enhancement (55%) was observed following the combination treatment in the obese animals. Enhanced levels of IRS-1 protein expression following 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 insulinresistant skeletal muscle following R-ALA or ET, alone and in combination, were associated with increases in IRS-1 protein expression and IRS-1 associated with p85.




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