Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase.
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.
Zheng
D
D
Department of Biochemistry, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA.
MacLean
P S
PS
Pohnert
S C
SC
Knight
J B
JB
Olson
A L
AL
Winder
W W
WW
Dohm
G L
GL
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D051275:Glucose Transporter Type 4; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D064326:MEF2 Transcription Factors; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009097:Multienzyme Complexes / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D018006:Myogenic Regulatory Factors; D011401:Promoter Regions, Genetic / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*
D004268:DNA-Binding Proteins; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D064326:MEF2 Transcription Factors; D009004:Monosaccharide Transport Proteins; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D018006:Myogenic Regulatory Factors; D012333:RNA, Messenger; D012265:Ribonucleotides; C495692:SLC2A4 protein, human; C495693:Slc2a4 protein, mouse; C495694:Slc2a4 protein, rat; D014157:Transcription Factors; D000620:Aminoimidazole Carboxamide; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide