Figure 3. Multiple, partly identical, pathways have been described to be activated by the GHR, the INSR and many other hormone kinase receptors not shown on the slide. Limiting this cartoon to the GHR and INSR, still the complexity is very high and the potential candidate hubs for crosstalk are numerous. The crosstalk that, following activation of the GHR, leads to resistance to specific signaling events from the INSR (related to glucose metabolism) is more well established and describe in detail in the Endotext chapter ‘Normal Physiology of Growth Hormone in Adults´. In the current review the focus is on the crosstalk that is executed by activation of the INSR and results in enhanced signaling from the GHR leading to gene activation of IGF1 and other GH dependent genes such as IGFBP3 and ALS. There are basically no studies addressing this crosstalk on the cellular level despite the strong evidence for INSR signaling being permissive for IGF1 transcription. Given that mTORC1 and mTORC2, downstream the INSR, are essential hubs for substrate and energy sensing and thus controlling the switch between cell anabolism and catabolism, they appear to be strong candidates to determine whether IGF1 should be on or off. A further argument for their candidate role is the so far limited evidence of mTORC1 and mTORC2 involvement in branched chain amino acid sensing directly enhancing IGF1 transcription. The unique role of the Jak2, STAT5b pathway in connecting the GHR with IGF1 gene activation has not been challenged and is thus the major candidate pathway to be affected by INSR signaling crosstalk. It is less clear which of the signaling pathways from the GHR that results in enhanced lipolysis although the STAT5b pathways has been implicated. This is particularly interesting given that GHR induced lipolysis does not require INSR signaling crosstalk. The reader is encouraged to seek specific information regarding other GHR and INSR pathways depicted in the cartoon but not further discussed in this review.