Sulfonylureas stimulate glucose uptake through GLUT4 transporter translocation in rat skeletal muscle

We studied the effect of gliclazide on glucose uptake and GLUT4 translocation in skeletal muscle. Rat hindquarters were perfused in the absence or presence of gliclazide (300 micrograms/ml), insulin or both drugs. The basal glucose uptake was increased 2.7-fold by gliclazide (p < 0.05). Gastrocnemius muscles perfused with gliclazide had a significant increase (2.4-fold) in the GLUT4 content in plasma membranes compared to basal conditions (p < 0.05). The stimulations produced by 1 nM insulin on muscle glucose uptake (2.8-fold) and on GLUT4 level in plasma membranes (2.5-fold) were similar to those produced by gliclazide. The effect of insulin on the glucose uptake and on the GLUT 4 translocation was significantly enhanced by gliclazide (3.4-fold and 3.7-fold vs basal, respectively). These data show that sulfonylureas stimulate glucose uptake in skeletal muscle by promoting the movement of GLUT4 to the plasma membrane.