Effects of clenbuterol on insulin resistance in conscious obese Zucker rats.
The present study was conducted to determine the effect of chronic administration of the long-acting beta(2)-adrenergic agonist clenbuterol on rats that are genetically prone to insulin resistance and impaired glucose tolerance. Obese Zucker rats (fa/fa) were given 1 mg/kg of clenbuterol by oral intubation daily for 5 wk. Controls received an equivalent volume of water according to the same schedule. At the end of the treatment, rats were catheterized for euglycemic-hyperinsulinemic (15 mU insulin. kg(-1). min(-1)) clamping. Clenbuterol did not change body weight compared with the control group but caused a redistribution of body weight: leg muscle weights increased, and abdominal fat weight decreased. The glucose infusion rate needed to maintain euglycemia and the rate of glucose disappearance were greater in the clenbuterol-treated rats. Furthermore, plasma insulin levels were decreased, and the rate of glucose uptake into hindlimb muscles and abdominal fat was increased in the clenbuterol-treated rats. This increased rate of glucose uptake was accompanied by a parallel increase in the rate of glycogen synthesis. The increase in muscle glucose uptake could not be ascribed to an increase in the glucose transport protein GLUT-4 in clenbuterol-treated rats. We conclude that chronic clenbuterol treatment reduces the insulin resistance of the obese Zucker rat by increasing insulin-stimulated muscle and adipose tissue glucose uptake. The improvements noted may be related to the repartitioning of body weight between tissues.
Exercise Physiology and Metabolism Laboratory, Department of Kinesiology and Health Education, University of Texas at Austin, Austin, TX 78712, USA.
S J
SJ
Pan
J
J
Hancock
Z
Z
Ding
D
D
Fogt
M
M
Lee
J L
JL
Ivy
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002976:Clenbuterol / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker; D014280:Triglycerides / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D006003:Glycogen; D005947:Glucose; D002976:Clenbuterol