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J Appl Physiol (November 30, 2001). doi:10.1152/japplphysiol.01009.2001
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Articles in PresS, published online ahead of print November 30, 2001
J Appl Physiol, 10.1152/jap.01009.2001
Submitted on October 3, 2001
Accepted on November 27, 2001

Clenbuterol prevents epinephrine from antagonizing insulin-stimulated muscle glucose uptake

Desmond H Hunt1, Zhenping Ding1, and John L Ivy1*

1 Kinesiology and Health Education, The University of Texas, Austin, Texas, USA

* To whom correspondence should be addressed. E-mail: johnivy{at}mail.utexas.edu.

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 IRS-1/PI 3-kinase activity. Clenbuterol treatment had no direct effect on insulin-stimulated glucose uptake. However, following 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-phophate and attenuate IRS-1/PI 3-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 pre-treated with clenbuterol.




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