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J Appl Physiol 91: 1073-1083, 2001;
8750-7587/01 $5.00
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Vol. 91, Issue 3, 1073-1083, September 2001

Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase

Donghai Zheng1, Paul S. MacLean1, Steven C. Pohnert1, John B. Knight2, Ann Louise Olson2, William W. Winder3, and G. Lynis Dohm1

1 Department of Biochemistry, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27858; 2 Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73190; and 3 Department of Zoology, Brigham Young University, Provo, Utah 84602

Skeletal muscle GLUT-4 transcription in response to treatment with 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside (AICAR), a known activator of AMP-activated protein kinase (AMPK), was studied in rats and mice. The increase in GLUT-4 mRNA levels in response to a single subcutaneous injection of AICAR, peaked at 13 h in white and red quadriceps muscles but not in the soleus muscle. The mRNA level of chloramphenicol acyltransferase reporter gene which is driven by 1,154 or 895 bp of the human GLUT-4 proximal promoter was increased in AICAR-treated transgenic mice, demonstrating the transcriptional upregulation of the GLUT-4 gene by AICAR. However, this induction of transcription was not apparent with 730 bp of the promoter. In addition, nuclear extracts from AICAR-treated mice bound to the consensus sequence of myocyte enhancer factor-2 (from -473 to -464) to a greater extent than from saline-injected mice. Thus AMP-activated protein kinase activation by AICAR increases GLUT-4 transcription by a mechanism that requires response elements within 895 bp of human GLUT-4 proximal promoter and that may be cooperatively mediated by myocyte enhancer factor-2.

myocyte enhancer factor-2; GLUT-4 promoter; transgenic mice; muscle fiber type


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