Division of Biochemistry, Central Drug Research Institute, Council of Scientific and Industrial Research, M.G. Road, Lucknow 226001, India. akhilesh
Mol Cell Endocrinol. 2011 Jun 6;339(1-2):98-104. doi: 10.1016/j.mce.2011.03.023. Epub 2011 Apr 8.
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.
骨骼肌是餐后葡萄糖处置的主要部位，增加葡萄糖向该组织的摄取可能会减弱 2 型糖尿病前期的胰岛素抵抗。在这里，我们研究了从印楝果实中鉴定出的先导化合物 pongamol 对骨骼肌细胞葡萄糖摄取和 GLUT4 易位的影响。在 L6-GLUT4myc 肌管中，pongamol 以浓度依赖的方式显著促进葡萄糖转运和 GLUT4 向细胞表面的易位，而不改变 GLUT4 蛋白和 GLUT4 mRNA 的总量，这些作用与胰岛素也具有相加作用。细胞松弛素处理抑制了 pongamol 对 GLUT4 易位的作用，表明需要新的蛋白质合成。wortmannin 完全消除了 pongamol 诱导的 GLUT4 易位增加，pongamol 显著增强了胰岛素介导的 AKT（Ser-473）磷酸化。我们得出结论，pongamol 诱导的 L6 肌管葡萄糖摄取增加是 GLUT4 向质膜易位增加的结果，这是由 PI-3-K/AKT 依赖的机制驱动的。
