Clenbuterol prevents epinephrine from antagonizing insulin-stimulated muscle glucose uptake

In the present study, we investigated the effects of chronic clenbuterol treatment on insulin-stimulated glucose uptake in the presence of epinephrine in isolated rat skeletal muscle. Insulin (50 μU/ml) increased glucose uptake in both fast-twitch (epitrochlearis) and slow-twitch (soleus) muscles. In the presence of 24 nM epinephrine, insulin-stimulated glucose uptake was completely suppressed. This suppression of glucose uptake by epinephrine was accompanied by an increase in the intracellular concentration of glucose 6-phosphate and a decrease in insulin-receptor substrate-1-associated phosphatidylinositol 3-kinase (IRS-1/PI3-kinase) activity. Clenbuterol treatment had no direct effect on insulin-stimulated glucose uptake. However, after clenbuterol treatment, epinephrine was ineffective in attenuating insulin-stimulated muscle glucose uptake. This ineffectiveness of epinephrine to suppress insulin-stimulated glucose uptake occurred in conjunction with its inability to increase the intracellular concentration of glucose 6-phosphate and attenuate IRS-1/PI3-kinase activity. Results of this study indicate that the effectiveness of epinephrine to inhibit insulin-stimulated glucose uptake is severely diminished in muscle from rats pretreated with clenbuterol.

Chronic administration of therapeutic levels of clenbuterol acts as a repartitioning agent

The purpose of this study was to examine the effect of therapeutic levels of clenbuterol, with and without exercise training, on body composition. Twenty-three unfit Standardbred mares were divided into four experimental groups: clenbuterol (2.4 μg/kg body wt twice daily) plus exercise (ClenEx; 20 min at 50% maximal oxygen consumption 3days/wk; n = 6), clenbuterol only (Clen; n = 6), exercise only (Ex; n = 5), and control (Con; n = 6). Rump fat thickness was measured at 2-wk intervals by using B-mode ultrasound, and percent body fat (%fat) was calculated by using previously published methods. For Ex, body fat decreased ( P < 0.05) at week 4 (−9.3%), %fat at week 6 (−6.9%), and fat-free mass (FFM) increased ( P < 0.05) at week 8 (+3.2%). On the other hand, Clen had significant changes in %fat (−15.4%), fat mass (−14.7%), and FFM (+4.3%) at week 2. ClenEx had significant decreases in %fat (−17.6%) and fat mass (−19.5%) at week 2, which was similar to Clen; however, this group had a different FFM response, which significantly increased (+4.4%) at week 6. Con showed no changes ( P > 0.05) in any variable at any time. These results suggest that exercise training and clenbuterol have additive effects with respect to %fat and fat mass but antagonistic effects in terms of FFM. Furthermore, chronic clenbuterol administration causes significant repartitioning in the horse, even when administered in therapeutic doses.