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Publication : Overexpression of peroxisome proliferator-activated receptor gamma coactivator-1alpha down-regulates GLUT4 mRNA in skeletal muscles.

First Author  Miura S Year  2003
Journal  J Biol Chem Volume  278
Issue  33 Pages  31385-90
PubMed ID  12777397 Mgi Jnum  J:84880
Mgi Id  MGI:2670495 Doi  10.1074/jbc.M304312200
Citation  Miura S, et al. (2003) Overexpression of peroxisome proliferator-activated receptor gamma coactivator-1alpha down-regulates GLUT4 mRNA in skeletal muscles. J Biol Chem 278(33):31385-90
abstractText  Exercise training increases mitochondria and GLUT4 in skeletal muscles. Recent studies indicate that an increased expression of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) by exercise may promote mitochondrial biogenesis and fatty acid oxidation. To examine whether increased PGC-1alpha expression was also responsible for an increase of GLUT4 expression, transgenic mice that overexpress PGC-1alpha in skeletal muscles driven by a human alpha-skeletal actin promoter were made. PGC-1alpha was overexpresssed in skeletal muscles including type I and II fiber-rich muscles but not in the heart. With an increase of PGC-1alpha mRNA, type II fiber-rich muscles were redder, and genes of mitochondrial oxidative metabolism were up-regulated in skeletal muscles, whereas the expression of GLUT4 mRNA was unexpectedly down-regulated. In parallel with a decrease of GLUT4 mRNA, an impairment of glycemic control after intraperitoneal insulin administration was observed. Thus, an increase of PGC-1alpha plays a role in increasing mitochondrial biogenesis and fatty acid oxidation but not in increasing GLUT4 mRNA in skeletal muscles.
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