Exercise training and clenbuterol reduce insulin resistance of obese Zucker rats

This study compared the effects of aerobic exercise training and chronic administration of the selective β₂-adrenergic agonist clenbuterol on whole body and skeletal muscle insulin resistance in obese (fa/fa) Zucker rats. Obese rats were randomly assigned to training, clenbuterol, or sedentary control groups. Lean littermates served as a second control group. After 4-5 wk of treatment, an oral glucose tolerance test was performed, followed 1 wk later by hindlimb perfusion, during which time the rates of glucose uptake and 3-O-methyl-D-glucose (3-MG) transport were assessed in the presence of a submaximal (500 μU/ml) insulin concentration. Training resulted in a significant increase in citrate synthase and cytochrome oxidase activity in the recruited muscles. Clenbuterol induced a large increase in muscle mass but provoked a significant decrease in oxidative enzyme activity and β- adrenergic receptor density. Both treatments increased glucose tolerance and reduced the postglucose insulin response, with the improvements being more pronounced in the clenbuterol group. However, only exercise training improved insulin-stimulated hindlimb muscle glucose uptake (11.37 ± 0.65, 8.73 ± 0.77, and 8.27 ± 0.41 μmol · g^-1 · h^-1 for trained, clenbuterol, and sedentary control groups, respectively) and 3-MG transport. These results suggest that aerobic exercise training attenuated the insulin-resistant condition in the obese Zucker rat by a mechanism other than or in addition to β₂-adrenergic receptor activation.