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J Appl Physiol 88: 2219-2226, 2000;
8750-7587/00 $5.00
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Vol. 88, Issue 6, 2219-2226, June 2000

Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle

W. W. Winder, B. F. Holmes, D. S. Rubink, E. B. Jensen, M. Chen, and J. O. Holloszy

Department of Zoology, Brigham Young University, Provo, Utah 84602; and Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110

Muscle contraction causes an increase in activity of 5'-AMP-activated protein kinase (AMPK). This study was designed to determine whether chronic chemical activation of AMPK will increase mitochondrial enzymes, GLUT-4, and hexokinase in different types of skeletal muscle of resting rats. In acute studies, rats were subcutaneously injected with either 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside (AICAR; 1 mg/g body wt) in 0.9% NaCl or with 0.9% NaCl alone and were then anesthetized for collection and freezing of tissues. AMPK activity increased in the superficial, white region of the quadriceps and in soleus muscles but not in the deep, red region of the quadriceps muscle. Acetyl-CoA carboxylase (ACC) activity, a target for AMPK, decreased in all three muscle types in response to AICAR injection but was lowest in the white quadriceps. In rats given daily, 1 mg/g body wt, subcutaneous injections of AICAR for 4 wk, activities of citrate synthase, succinate dehydrogenase, and malate dehydrogenase were increased in white quadriceps and soleus but not in red quadriceps. Cytochrome c and delta -aminolevulinic acid synthase levels were increased in white, but not red, quadriceps. Carnitine palmitoyl-transferase and hydroxy-acyl-CoA dehydrogenase were not significantly increased. Hexokinase was markedly increased in all three muscles, and GLUT-4 was increased in red and white quadriceps. These results suggest that chronic AMPK activation may mediate the effects of muscle contraction on some, but not all, biochemical adaptations of muscle to endurance exercise training.

delta -aminolevulinate synthase; carnitine palmitoyl transferase; citrate synthase; citric acid cycle enzymes; endurance training; GLUT-4; muscle mitochondria


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