The MEF2A and MEF2D isoforms are differentially regulated in muscle and adipose tissue during states of insulin deficiency

Previously we have demonstrated that striated muscle GLUT4 gene expression decreased following streptozotocin-induced diabetes due to a loss of MEF2A transcription factor expression without any significant effect on the MEF2D isoform (Mora, S. and J. E. Pessin (2000) J Biol Chem, 275:16323-16328). I n contrast to both cardiac and skeletal muscle, adipose tissue displays a s elective decrease in MEF2D expression in diabetes without any significant a lteration in MEF2A protein content. Adipose tissue also expresses very low levels of the MEF2 transcription factors and nuclear extracts from white ad ipose tissue exhibit poor in vitro binding to the MEF2 element. However, ad dition of in vitro synthesized MEF2A to adipose nuclear extracts results in the formation of the expected MEF2/DNA complex. More importantly, binding to the MEF2 element was also compromised in the diabetic condition. Further more, in vivo overexpression of MEF2A selectively in adipose tissue did not affect GLUT4 or MEF2D expression and was not sufficient to prevent GLUT4 d ownregulation that occurred in insulin-deficient states.