Interactions of exercise training and the antioxidant alpha-lipoic acid on insulin action in obese Zucker rats

Abstract

The insulin resistance syndrome is a multifaceted condition characterized by a clustering of metabolic and cardiovascular abnormalities, including insulin resistance of skeletal muscle glucose metabolism, hyperinsulinemia, glucose intolerance, dyslipidemia, essential hypertension, and central adiposity. Individual interventions with antioxidants or endurance exercise training enhanced insulin action on skeletal muscle and whole body insulin sensitivity in the markedly insulin-resistant, hyperinsulinemic, and dyslipidemic obese Zucker (fa/fa) rat. Individually, antioxidant treatment and exercise training by the obese Zucker rat resulted in a decrease in protein carbonyls (reflective of local oxidative stress), plasma free fatty acids, and intramuscular triglycerides, as well as an upregulation of the protein expression of insulin receptor substrate-1 (IRS-1), a critical component of the insulin signaling pathway. Whereas exercise training alone enhanced the protein expression of GLUT-4 glucose transporter isoform, this protein expression was not affected by antioxidant treatment. Most importantly, this study has investigated the interactions of antioxidant and exercise training in combination on whole body insulin sensitivity and skeletal muscle insulin action in the obese Zucker rat. The combination of antioxidant and exercise training functioned in an additive fashion and brought about the greatest increases in insulin action on skeletal muscle glucose transport activity and IRS-1 protein expression compared with either intervention individually. In addition, the IRS-1 protein expression, following the individual or combined intervention of antioxidant and exercise training, was correlated with insulin-mediated glucose transport in skeletal muscle. It is therefore likely that, in response to insulin, the downstream signaling from the expanded IRS-1 protein pool, in skeletal muscle from obese Zucker rats treated with antioxidant and exercise training in combination, acts on the expanded GLUT-4 pool (derived from exercise training) to bring about the greatest incorporation of GLUT-4 into the plasma membrane, with a corresponding enhancement of glucose transport activity. This study supports the utility of the combination of exercise training and antioxidant for the prevention and treatment of insulin resistance and type 2 diabetes.