Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1, Komatsushima, Aoba-ku, Sendai 981-8558, Miyagi, Japan.
FEBS Lett. 2012 Jan 20;586(2):191-5. doi: 10.1016/j.febslet.2011.12.019. Epub 2011 Dec 22.
Previously, we demonstrated that an inhibitor of ganglioside biosynthesis, d-PDMP, could restore impaired insulin signaling in tumor necrosis factor α (TNFα)-treated adipocytes by blocking the increase of GM3 ganglioside. Here, we analyzed the interaction between insulin receptor (IR) and GM3 in the plasma membranes using immunoelectron microscopy. In normal adipocytes, most GM3 molecules localized at planar and non-caveolar regions. Approximately 19% of IR molecules were detected in caveolar regions. The relative ratio of IRs associated with caveolae in TNFα-treated adipocytes was decreased to one-fifth of that in normal adipocytes, but this decrease was restored by d-PDMP. Thus, we could obtain direct evidence that insulin resistance is a membrane microdomain disorder caused by aberrant expression of ganglioside.
此前，我们证明了 ganglioside 生物合成抑制剂 d-PDMP 可以通过阻断 GM3 神经节苷脂的增加来恢复肿瘤坏死因子 α (TNFα) 处理的脂肪细胞中受损的胰岛素信号。在这里，我们使用免疫电子显微镜分析了胰岛素受体 (IR) 和 GM3 在质膜中的相互作用。在正常的脂肪细胞中，大多数 GM3 分子定位于平面和非 caveolar 区域。在 caveolar 区域中检测到约 19%的 IR 分子。TNFα 处理的脂肪细胞中与 caveolae 相关的 IR 相对比例降至正常脂肪细胞的五分之一，但这一减少被 d-PDMP 所恢复。因此，我们可以获得直接证据表明，胰岛素抵抗是一种由神经节苷脂异常表达引起的膜微区紊乱。
