Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1.
Muscle tissue is the major site for insulin-stimulated glucose uptake in vivo, due primarily to the recruitment of the insulin-sensitive glucose transporter (GLUT4) to the plasma membrane. Surprisingly, virtually all cultured muscle cells express little or no GLUT4. We show here that adenovirus-mediated expression of the transcriptional coactivator PGC-1, which is expressed in muscle in vivo but is also deficient in cultured muscle cells, causes the total restoration of GLUT4 mRNA levels to those observed in vivo. This increased GLUT4 expression correlates with a 3-fold increase in glucose transport, although much of this protein is transported to the plasma membrane even in the absence of insulin. PGC-1 mediates this increased GLUT4 expression, in large part, by binding to and coactivating the muscle-selective transcription factor MEF2C. These data indicate that PGC-1 is a coactivator of MEF2C and can control the level of endogenous GLUT4 gene expression in muscle.
Michael
L F
LF
Dana-Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Wu
Z
Z
Cheatham
R B
RB
Puigserver
P
P
Adelmant
G
G
Lehman
J J
JJ
Kelly
D P
DP
Spiegelman
B M
BM
D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000502:physiology; D064326:MEF2 Transcription Factors; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D018006:Myogenic Regulatory Factors / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D014157:Transcription Factors / Q000737:chemistry / Q000494:pharmacology*
D051275:Glucose Transporter Type 4; D007328:Insulin; D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D018006:Myogenic Regulatory Factors; C495693:Slc2a4 protein, mouse; C495694:Slc2a4 protein, rat; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D005947:Glucose