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 beta 2-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 microU/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 beta-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 mumol.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 beta 2-adrenergic receptor activation.
Torgan
C E
CE
Department of Kinesiology, University of Texas, Austin 78712.
Brozinick
J T
JT
Banks
E A
EA
Cortez
M Y
MY
Wilcox
R E
RE
Ivy
J L
JL
D019325:3-O-Methylglucose; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002950:Citrate (si)-Synthase / Q000032:analysis / Q000502:physiology; D002976:Clenbuterol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV / Q000032:analysis / Q000502:physiology; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics / Q000494:pharmacology; D005951:Glucose Tolerance Test; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008757:Methylglucosides / Q000493:pharmacokinetics; D009132:Muscles / Q000201:enzymology / Q000502:physiology / Q000648:ultrastructure; D009765:Obesity / Q000503:physiopathology*; D010805:Physical Conditioning, Animal; D051381:Rats; D011924:Rats, Zucker; D011941:Receptors, Adrenergic / Q000032:analysis
D007328:Insulin; D008757:Methylglucosides; D011941:Receptors, Adrenergic; D019325:3-O-Methylglucose; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D005947:Glucose; D002976:Clenbuterol