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 vi vo, due primarily to the recruitment of the insulin-sensitive glucose trans porter (GLUT4) to the plasma membrane. Surprisingly, virtually all cultured muscle cells express little or no GLUT4, We show here that adenovirus-medi ated expression of the transcriptional coactivator PGC-1, which is expresse d 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 tra nsport, although much of this protein is transported to the plasma membrane even in the absence of insulin. PGC-1 mediates this increased GLUT4 expres sion, in large part, by binding to and coactivating the muscle-selective tr anscription factor MEF2C, These data indicate that PGC-1 is a coactivator o f MEF2C and can control the level of endogenous GLUT4 gene expression in mu scle.