We studied the effects of exercise on GLUT4 gene transcription in several lines of transgenic mice expressing the chloramphenicol acyltransferase (CAT) reporter gene, driven by various lengths of the human GLUT4 promoter (2400, 1600, 895, and 730 bp). In all transgenic lines examined, endogenous GLUT4 mRNA increased in response to exercise (19-90%, P < 0.05). Exercise increased CAT mRNA (51-83%, P < 0.05) in mice when the transgene was driven by at least 895 by of the promoter but showed no effect in mice in which the transgene was driven by only 730 bp. These results suggest that the exercise-induced increase in the transcriptional activity of the human GLUT4 gene is mediated, at least in part, by element(s) within -895 bp of the promoter. These observations reveal a striking similarity to the time course and regional promoter requirements of AMPK-induced GLUT4 gene expression, providing further evidence that AMPK may be mediating the effects of exercise on GLUT4 expression. (C) 2002 Elsevier Science (USA)