SKELETAL-MUSCLE GLUCOSE-TRANSPORT AND METABOLISM ARE ENHANCED IN TRANSGENIC MICE OVEREXPRESSING THE GLUT4 GLUCOSE-TRANSPORTER

Skeletal muscle glucose transport and metabolism were studied in a lin e of transgenic mice overexpressing the human Glut4 facilitative gluco se transporter, Skeletal muscle Glut4 protein levels were increased 2- 4-fold in transgenic animals relative to their nontransgenic litter ma tes, Glut4 overexpression increased total transport activity (measured with 1 mM a deoxy-D-glucose) in the isolated extensor digitorum brevi s muscle in the presence of insulin; this increase was due to 1) an in crease in basal glucose transport (0.8 +/- 0.1 versus 0.5 +/- 0.1 mu m ol.ml(-1).20 min(-1) in transgenic and control mice, respectively) and 2) an increase in insulin-stimulated transport (1.5 +/- 0.1 versus 0. 8 +/- 0.1 mu mol.ml(-1).20 min(-1) above basal transport in transgenic and control mice, respectively), Glut4 overexpression also increased glucose transport stimulated by muscle contractions. In addition, glyc olysis and glucose incorporation into glycogen were enhanced in muscle isolated from transgenic mice compared to controls, These data demons trate that Glut4 overexpression in skeletal muscle increases insulin a nd contraction-stimulated glucose transport activity and glucose metab olism, These findings are consistent with the role of Glut4 as the pri mary mediator of transport stimulated by insulin or contractions.