van den Berghe N, Barros L F, van Mackelenbergh M G, Krans H M
Department of Endocrinology, University Hospital Leiden, The Netherlands.
Biochem Biophys Res Commun. 1996 Dec 13;229(2):430-9. doi: 10.1006/bbrc.1996.1821.
The signal transduction pathway by which insulin stimulates glucose transport is largely unknown, but a role of PI-3-kinase and small GTP-binding proteins has been proposed. In previous studies we, among many others, excluded a role for the ras/MAP kinase pathway in insulin-mediated glucose transport. In this study we examined a possible role of the small GTP-binding protein rho in this process. Pretreatment of 3T3-L1 adipocytes with botulinum C3 exoenzyme (C3), which is known to ADP-ribosylate and inactivate rho, potently stimulated glucose uptake to a level similar to insulin. Interestingly, glycogen synthesis was not affected by C3 treatment. Insulin stimulates glucose uptake by triggering the translocation of GLUT4, the insulin-sensitive glucose transporter isotype, from an intracellular compartment to the plasma membrane. Similarly, C3-induced glucose uptake was paralleled by GLUT4 translocation. These data point to an important and novel role of the target of C3 (likely rho) in the regulation of GLUT4-mediated glucose transport. Our data suggest that insulin might stimulate glucose uptake through inactivation of rho.
胰岛素刺激葡萄糖转运的信号转导途径很大程度上尚不清楚，但有人提出磷脂酰肌醇-3激酶（PI-3-激酶）和小GTP结合蛋白发挥了作用。在先前的研究中，我们和其他许多人一样，排除了ras/丝裂原活化蛋白激酶（MAP激酶）途径在胰岛素介导的葡萄糖转运中的作用。在本研究中，我们研究了小GTP结合蛋白rho在此过程中可能发挥的作用。用肉毒杆菌C3外毒素（C3）预处理3T3-L1脂肪细胞，已知该毒素可使rho ADP核糖基化并使其失活，能有效地刺激葡萄糖摄取，使其达到与胰岛素相似的水平。有趣的是，糖原合成不受C3处理的影响。胰岛素通过触发GLUT4（胰岛素敏感的葡萄糖转运蛋白亚型）从细胞内区室向质膜的转位来刺激葡萄糖摄取。同样，C3诱导的葡萄糖摄取与GLUT4转位同时发生。这些数据表明C3的靶标（可能是rho）在调节GLUT4介导的葡萄糖转运中具有重要的新作用。我们的数据表明，胰岛素可能通过使rho失活来刺激葡萄糖摄取。
