Rakatzi Irini, Stosik Magdalene, Gromke Tanja, Siddle Kenneth, Eckel Jürgen
Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany.
Arch Physiol Biochem. 2006 Feb;112(1):37-47. doi: 10.1080/13813450500500332.
The specific contribution of insulin and IGF-I receptors to IRS-protein activation remains elusive. We studied the signalling properties of AspB10-insulin, an analog with enhanced affinity for the IGF-I receptor, in comparison to native insulin using primary human skeletal muscle cells. In myoblasts regular insulin and AspB10-insulin were equipotent in stimulating the IRS cascade, whereas this analog induced a significantly higher Shc phosphorylation. Phosphorylation of IRS-1 in response to insulin was inhibited equally by blocking either the insulin or the IGF-I receptor. IRS-1 activation by AspB10-insulin was only inhibited by blocking the IGF-I receptor. IRS-2 phosphorylation induced by both insulin and AspB10-insulin was nearly insensitive to blocking the insulin receptor, being predominantly mediated by the IGF-I receptor. We conclude that in myoblasts IRS-2, but not IRS-1, functions as preferred substrate for the IGF-I receptor. These data suggest a specific role for IRS-2 in growth and differentiation of human skeletal muscle.
胰岛素和胰岛素样生长因子-I（IGF-I）受体对胰岛素受体底物（IRS）蛋白激活的具体贡献仍不清楚。我们使用原代人骨骼肌细胞，研究了与天然胰岛素相比，对IGF-I受体具有更高亲和力的类似物AspB10-胰岛素的信号特性。在成肌细胞中，常规胰岛素和AspB10-胰岛素在刺激IRS级联反应方面效力相当，而这种类似物诱导的Shc磷酸化显著更高。通过阻断胰岛素或IGF-I受体，均可同等程度地抑制胰岛素诱导的IRS-1磷酸化。AspB10-胰岛素激活IRS-1仅被阻断IGF-I受体所抑制。胰岛素和AspB10-胰岛素诱导的IRS-2磷酸化对阻断胰岛素受体几乎不敏感，主要由IGF-I受体介导。我们得出结论，在成肌细胞中，IRS-2而非IRS-1是IGF-I受体的优先作用底物。这些数据表明IRS-2在人类骨骼肌生长和分化中具有特定作用。
