Skeletal muscle is the major site of postprandial glucose disposal and augmenting glucose uptake into this tissue may attenuate insulin resistance that precedes type 2 diabetes mellitus. Here, we investigated the effect of pongamol, an identified lead molecule from the fruits of Pongamia pinnata, on glucose uptake and GLUT4 translocation in skeletal muscle cells. In L6-GLUT4myc myotubes treatment with pongamol significantly promoted both glucose transport and GLUT4 translocation to the cell surface in a concentration-dependent manner, without changing the total amount of GLUT4 protein and GLUT4 mRNA, effects that were also additive with insulin. Cycloheximide treatment inhibited the effect of pongamol on GLUT4 translocation suggesting the requirement of new protein synthesis. The pongamol-induced increase in GLUT4 translocation was completely abolished by wortmannin, and pongamol significantly potentiated insulin-mediated phosphorylation of AKT (Ser-473). We conclude that pongamol-induced increase in glucose uptake in L6 myotubes is the result of an increased translocation of GLUT4 to plasma membrane, driven by a PI-3-K/AKT dependent mechanism.
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