Interaction of aerobic exercise training and clenbuterol: effects on insulin-resistant muscle

• Published in: Journal of applied physiology (1985) Vol. 75; no. 4; p. 1471
• Main Authors: Torgan, C E, Etgen, Jr, G J, Brozinick, Jr, J T, Wilcox, R E, Ivy, J L
• Format: Journal Article
• Language: English
• Published: United States 01.10.1993
• Subjects: Aerobiosis - physiology; Animals; Body Weight - physiology; Citrate (si)-Synthase - metabolism; Clenbuterol - pharmacology; Enzymes - blood; Female; Glucose - metabolism; Hindlimb - blood supply; Insulin Resistance - physiology; Muscles - drug effects; Muscles - physiology; Obesity - physiopathology; Organ Size - physiology; Physical Conditioning, Animal; Rats; Rats, Zucker; Receptors, Adrenergic, beta - drug effects; Receptors, Adrenergic, beta - physiology; Regional Blood Flow - physiology
• ISSN: 8750-7587
• DOI: 10.1152/jappl.1993.75.4.1471

The effects of aerobic exercise training, chronic administration of the selective beta 2-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 trained, clenbuterol, clenbuterol-trained, or control groups. Training consisted of treadmill running for 2 h/day at 18 m/min up an 8% grade. Clenbuterol was administered by intubation (0.4-0.8 mg.kg body wt-1 x day-1) approximately 30 min before the rats ran each day. After 8 wk of treatment, muscle insulin resistance was assessed via hindlimb perfusion in the presence of 8 mM glucose and a submaximal (500 microU/ml) insulin concentration. Training increased citrate synthase activity (mumol.g wet wt-1 x min-1) by 32-74% and insulin-stimulated glucose uptake by 45%. Clenbuterol ingestion induced a 17-29% increase in muscle mass but decreased citrate synthase activity by 34-42% and had no effect on muscle glucose uptake. Administration of clenbuterol to rats that exercise trained prevented the training-induced improvement in insulin-stimulated glucose uptake and attenuated the increases in citrate synthase activity. In addition, both clenbuterol-treated groups displayed a 42% decrease in beta-adrenergic receptor density. The results indicate that clenbuterol administration, possibly through beta-adrenergic receptor downregulation, attenuated a cellular reaction essential for the exercise training-induced increase in citrate synthase activity and improvement in skeletal muscle insulin resistance of the obese Zucker rat.