INSERM, U895, Mediterranean Research Center for Molecular Medicine (C3M), Avenir Team 9, Nice, France.
PLoS One. 2010 Dec 20;5(12):e15560. doi: 10.1371/journal.pone.0015560.
In response to insulin, glucose transporter GLUT4 translocates from intracellular compartments towards the plasma membrane where it enhances cellular glucose uptake. Here, we show that sera from various species contain a factor that dose-dependently induces GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes, human adipocytes, myoblasts and myotubes. Notably, the effect of this factor on GLUT4 is fully maintained in insulin-resistant cells. Our studies demonstrate that the serum-induced increase in cell surface GLUT4 levels is not due to inhibition of its internalization and is not mediated by insulin, PDGF, IGF-1, or HGF. Similarly to insulin, serum also augments cell surface levels of GLUT1 and TfR. Remarkably, the acute effect of serum on GLUT4 is largely additive to that of insulin, while it also sensitizes the cells to insulin. In accordance with these findings, serum does not appear to activate the same repertoire of downstream signaling molecules that are implicated in insulin-induced GLUT4 translocation. We conclude that in addition to insulin, at least one other biological proteinaceous factor exists that contributes to GLUT4 regulation and still functions in insulin resistance. The challenge now is to identify this factor.
当人体受到胰岛素刺激时，葡萄糖转运蛋白 GLUT4 会从细胞内隔室转移到质膜，从而增强细胞对葡萄糖的摄取。在这里，我们发现来自不同物种的血清中含有一种因子，该因子可剂量依赖性地诱导 3T3-L1 脂肪细胞、人脂肪细胞、成肌细胞和肌管中的 GLUT4 易位和葡萄糖摄取。值得注意的是，该因子对 GLUT4 的作用在胰岛素抵抗细胞中完全保留。我们的研究表明，该因子诱导细胞表面 GLUT4 水平增加不是由于其内化的抑制，也不是由胰岛素、PDGF、IGF-1 或 HGF 介导的。与胰岛素类似，血清也增加 GLUT1 和 TfR 的细胞表面水平。值得注意的是，血清对 GLUT4 的急性作用在很大程度上与胰岛素的作用相加，同时也使细胞对胰岛素敏感。根据这些发现，血清似乎不会激活与胰岛素诱导的 GLUT4 易位相关的相同的下游信号分子谱。我们得出结论，除了胰岛素之外，至少还有另一种生物蛋白因子参与 GLUT4 的调节，并且在胰岛素抵抗中仍然发挥作用。现在的挑战是识别这种因子。
