Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase.
Zheng, Donghai, Paul S. MacLean, Steven C. Pohnert, John B. Knight, Ann Louise
Olson, William W. Winder, and G. Lynis Dohm.
1Department of Biochemistry, Brody School of Medicine, East Carolina University,
Greenville, North Carolina 27858; 2Department of Biochemistry and Molecular Biology,
University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73190; and
3Department of Zoology, Brigham Young University, Provo, Utah 84602
APStracts 8:0289A, 2001.
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 «minus»473 to «minus»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.
Received 8 December 2000; accepted in final form 30 April 2001
APS Manuscript Number A1173-0.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 18 June 2001