RELATIONSHIP BETWEEN INSULIN-STIMULATED GLUCOSE TRANSPORT AND OXIDATIVE STRESS IN INSULIN-RESISTANT RAT SKELETAL MUSCLE

Abstract

The obese Zucker (fa/fa) rat is an animal model of obesity-associated skeletal muscle insulin resistance, and also displays characteristics of oxidative stress. The purpose of the present investigation was to determine the responses of insulin-stimulated glucose transport and protein carbonyl levels (an index of oxidative stress) in the soleus muscle of female obese Zucker rats following 6 wk of sedentary housing (SED), exercise training (ET; treadmill running at 24–30 m/min, 4% grade, 70–90 min/day for 6 wk), treatment with the antioxidant R-(+)-alpha-lipoic acid (R-ALA; 30 mg/kg body wt/day for 6 wk), or the two interventions in combination (COMBO). Maximally-activated insulin-stimulated (2 mU/ml) glucose transport (2-deoxyglucose uptake) in soleus strips was increased (p < 0.05) relative to SED by ET alone (+57%) or R-ALA treatment alone (+37%), with the greatest improvement in insulin action (+99%) observed in the COMBO group. Soleus protein carbonyl levels were reduced relative to SED by ET alone (−32%) or R-ALA alone (−41%), with no further significant reduction (−44%) seen in the COMBO group. The correlation coefficient of the regression analysis between insulin-mediated glucose transport and protein carbonyl levels in the soleus from all of the groups combined was significant (r = 0.626). The results of this study indicate that reductions in muscle protein carbonyl levels following endurance exercise training or an antioxidant intervention are associated with improvements in insulin action on glucose transport. However, because the further improvement in insulin-stimulated glucose transport in the soleus from the COMBO group was not accompanied by a further reduction in oxidative stress, it is clear that this relationship is not a simple one, and additional, as yet unidentified, factors are responsible for this adaptive response in insulin action. Supported by AHA 9951103Z