INTERACTION OF AEROBIC EXERCISE TRAINING AND CLENBUTEROL - EFFECTS ONINSULIN-RESISTANT MUSCLE

The effects of aerobic exercise training, chronic administration of th e selective beta2-adrenergic agonist clenbuterol, and the combination of these two treatments on muscle insulin resistance were compared in female obese (fa/fa) Zucker rats. Rats were randomly assigned to train ed, clenbuterol, clenbuterol-trained, or control groups. Training cons isted of treadmill running for 2 h/day at 18 m/min up an 8% grade. Cle nbuterol was administered by intubation (0.4-0.8 mg - kg body wt-1 - d ay-1) approximately 30 min before the rats ran each day. After 8 wk of treatment, muscle insulin resistance was assessed via hindlimb perfus ion in the presence of 8 mM glucose and a submaximal (500 muU/ml) insu lin concentration. Training increased citrate synthase activity (mumol - g wet wt-1 - min-1) by 32-74% and insulin-stimulated glucose uptake by 45%. Clenbuterol ingestion induced a 17-29% increase in muscle mas s but decreased citrate synthase activity by 34-42% and had no effect on muscle glucose uptake. Administration of clenbuterol to rats that e xercise trained prevented the training-induced improvement in insulin- stimulated glucose uptake and attenuated the increases in citrate synt hase activity. In addition, both clenbuterol-treated groups displayed a 42% decrease in beta-adrenergic receptor density. The results indica te that clenbuterol administration, possibly through beta-adrenergic r eceptor downregulation, attenuated a cellular reaction essential for t he exercise training-induced increase in citrate synthase activity and improvement in skeletal muscle insulin resistance of the obese Zucker rat.