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Further, Potamitou et al

Attempts to improve linear growth by rhIGF-I treatment has been reported to result in some improvements in a few affected children but not all (134, 135) It is beyond the scope of this chapter to review the overwhelming evidence from cell biology experiments demonstrating the important role of IGFBPs in modulating IGF bioactivity and the role of IGFBP proteases and their actions at the cellular level

This metabolic switch is driven largely by the combined effects of signals 2 and 3 that stimulate signaling pathways, such as PI3K AKT MTORC1, and is regulated by TFs, including HIF1, MYC and STAT5 170, 171, 172

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