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. Author manuscript; available in PMC: 2020 Jul 1.
Published in final edited form as: Neurosci Biobehav Rev. 2019 May 16;102:345–361. doi: 10.1016/j.neubiorev.2019.05.012

Figure 2.

Figure 2.

Proposed mechanism by which TBI alters hypothalamic-pituitary growth hormone (GH) Axis. TBI-induced chronic growth hormone deficiency (GHD) is characterized by metabolic abnormalities associated with decreased IGF-1 synthesis. The presence of low plasma GH decreases the hepatic IGF-1 synthesis via dysregulation of the GH receptor, JAK2 and STAT5 pathways. Early hepatic inflammation after TBI also activates the hepatic toll like receptors (TLR-4) that leads to nuclear translocation of the transcription factor NF-κB, TNF-αreceptor upregulation and TNF-α increase. This systemic inflammation could induce insulin resistance by stimulating cytokines receptors and JNK pathway that leads to serine/threonine phosphorylation of IRS1, TNF-α and mitochondrial ROS production. It is recognized that the growth hormone GH/IGF system is involved in metabolism manifestations. In turn, TBI-induced GH/IGF-1 deficiency may be associated with visceral obesity that leads to systemic inflammation and ROS production. Low plasma IGF-1 induces β-cell exhaustion and consequently peripheral insulin resistance by dysregulation of the IGF-1 receptor, PDE and PKA pathway.