Effects of clenbuterol on insulin resistance in conscious obese Zucker rats

The present study was conducted to determine the effect of chronic administ ration of the long-acting beta (2)-adrenergic agonist clenbuterol on rats t hat are genetically prone to insulin resistance and impaired glucose tolera nce. Obese Zucker rats (fa/fa) were given 1 mg/kg of clenbuterol by oral in tubation daily for 5 wk. Controls received an equivalent volume of water ac cording to the same schedule. At the end of the treatment, rats were cathet erized for euglycemic-hyperinsulinemic (15 mU insulin.kg(-1).min(-1)) clamp ing. 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 mai ntain 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 wa s increased in the clenbuterol-treated rats. This increased rate of glucose uptake was accompanied by a parallel increase in the rate of glycogen synt hesis. The increase in muscle glucose uptake could not be ascribed to an in crease in the glucose transport protein GLUT-4 in clenbuterol-treated rats. We conclude that chronic clenbuterol treatment reduces the insulin resista nce of the obese Zucker rat by increasing insulin-stimulated muscle and adi pose tissue glucose uptake. The improvements noted may be related to the re partitioning of body weight between tissues.