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.
Pan
S J
SJ
Exercise Physiology and Metabolism Laboratory, Department of Kinesiology and Health Education, University of Texas at Austin, Austin, TX 78712, USA.
Hancock
J
J
Ding
Z
Z
Fogt
D
D
Lee
M
M
Ivy
J L
JL
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