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J Appl Physiol 92: 1285-1292, 2002. First published November 30, 2001; doi:10.1152/japplphysiol.01009.2001
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Vol. 92, Issue 3, 1285-1292, March 2002

Clenbuterol prevents epinephrine from antagonizing insulin-stimulated muscle glucose uptake

Desmond G. Hunt, Zhenping Ding, and John L. Ivy

Exercise Physiology and Metabolism Laboratory, Department of Kinesiology and Health Education, University of Texas at Austin, Austin, Texas 78712

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.

glucose 6-phosphate; phosphatidylinositol 3-kinase; glycogen; beta -adrenergic receptors; propranolol


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