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J Appl Physiol 91: 2102-2108, 2001;
8750-7587/01 $5.00
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Vol. 91, Issue 5, 2102-2108, November 2001

AMP-activated protein kinase activation prevents denervation-induced decline in gastrocnemius GLUT-4

S. R. Paulsen, D. S. Rubink, and W. W. Winder

Department of Zoology, Brigham Young University, Provo, Utah 84602

This study was designed to determine whether the reductions in GLUT-4 seen in 3-day-denervated muscles can be prevented through chemical activation of 5'-AMP-activated protein kinase (AMPK). Muscle AMPK can be chemically activated in rats using subcutaneous injections with 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside (AICAR). In this study, the tibial nerve was sectioned on one side; the other was sham operated but without nerve section. Acute injections of AICAR resulted in significantly increased AMPK activity in denervated gastrocnemius but not soleus muscles. Acetyl-CoA carboxylase activity, a reporter of AMPK activation, declined in both gastrocnemius and soleus in both denervated and contralateral muscles. Three days after denervation, GLUT-4 levels were significantly decreased by ~40% in gastrocnemius muscles and by ~30% in soleus muscles. When rats were injected with AICAR (1 mg/g body wt) for 3 days, the decline in GLUT-4 levels was prevented in denervated gastrocnemius muscles but not in denervated soleus muscles. The extent of denervation-induced muscle atrophy was similar in AICAR-treated vs. saline-treated rats. These studies provide evidence that some effects of denervation may be prevented by chemical activation of the appropriate signaling pathways.

5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside; adenosine 5'-monophosphate; acetyl-coenzyme A carboxylase; glucose transport; contraction


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