Interaction of aerobic exercise training and clenbuterol: effects on insulin-resistant muscle.
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.
Torgan
C E
CE
Department of Kinesiology, University of Texas, Austin 78712.
Etgen
G J
GJ
Brozinick
J T
JT
Wilcox
R E
RE
Ivy
J L
JL
D000332:Aerobiosis / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002950:Citrate (si)-Synthase / Q000378:metabolism; D002976:Clenbuterol / Q000494:pharmacology*; D004798:Enzymes / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply; D007333:Insulin Resistance / Q000502:physiology*; D009132:Muscles / Q000187:drug effects / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology; D009929:Organ Size / Q000502:physiology; D010805:Physical Conditioning, Animal; D051381:Rats; D011924:Rats, Zucker; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology
D004798:Enzymes; D011943:Receptors, Adrenergic, beta; D002950:Citrate (si)-Synthase; D005947:Glucose; D002976:Clenbuterol