IGF1

Official Full Name

insulin like growth factor 1

Organism

Homo sapiens

GeneID

3479

Background

The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]

Synonyms

IGF; MGF; IGFI; IGF-I;

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Detailed Information

Insulin like growth factor（IGF）system has been attracting the attention of researchers in most biology field since it is one of the most pervasive systems in biology. IGF1, the key factor among the IGF system, works in by binding to IGF1 receptor (IGF1R) or /and various IGF binding proteins.

IGF1 signaling pathway

Binding of IGF1 to the IGF1R leads to autophosphorylation of tyrosine residues and the recruitment of adapter proteins such as the IRS-1/IRS-2, as well as the SH2 domain-containing proteins usually. The alteration of IRS-1 and IRS-2 induces an intracellular signaling cascade in at least two pathways. One is the phosphatidyl-inositol-3-kinase pathway (PI3-K), and another is mitogen-activated protein kinase (MAPK) pathway as illustrated in Figure 1. Thus, not only normal physiological process such as cellular pathways, tissue metabolism, but also a wide array of abnormal physiological process including neuropsychiatric disorders, diabetes and cancer, to name but a few.

Figure 1. Commonly accepted intracellular signaling mechanisms of IGF/insulin.
(Fumihiko Hakuno et al. 2018)

While IGF1 is produced by many tissues such as skeletal muscle, the brain, cartilage and pancreas, its main source is liver. Some reports have revealed that that circulating IGF1 regulates hepatocyte metabolism indirectly through modulation of hormonal inputs like reducing the GH secretion. Experiments in all species have shown that IGF1 does act directly at the level of the somatotrope to suppress GH gene transcription in primary pituitary cell cultures, including primate. Moreover, studies also show that the IGF1 effects in enhancing pancreatic β-cell function, supporting thyroid hormone production, and the development of granulosa cell (estrogen) through IGF1R.

IGF1 and neuropsychiatric diseases

The influence of IGF1 in the behavior of even other neurotrophic factors and neurotransmitters also comes the focus. The IGF-1 cell pathway disruption, its receptors or serum IGF-1 levels, has been seen as an important factor triggering various neuropsychiatric diseases such as depression, anxiety, post-traumatic stress disorder, neurodegenerative disorders and autism. Circulating IGF1 produced by liver can also enter the brain to exercise its properties. Researches on IGF1 show that its role in the control and regulation of mood may in relation to its implication in processes such as synaptic plasticity, cell differentiation and neurogenesis. In addition, studies about mechanisms linking IGF-1 and PTSD indicate that successive deregulation of the HPA axis by a decrease in neurotrophic agents especially IGF-1, the hippocampal atrophy by adrenal steroids, as well as a possible altered IGF-1 activity in the adenohypophysis is the reason of a decrease in adult hypothalamic neurogenesis. As to Alzheimer's disease, Westwood found that its higher incidence in older adults are associated with reduced levels of serum IGF-1. Moreover, studies about the amounts of IGF1 in the cerebrospinal fluid of children with autism suggest that there is a significant decrease of this trophic factor in comparison to the controls.

Summary

Apart from the effects of IGF1 mentioned above, it also plays an important role in mediating exercise-induced cardiac hypertrophy and protection via the IGF1-PI3K-Akt signaling pathway, according to the researches in genetically modified mice models. Additionally, IGF1 is also a crucial factor for bone cell function and skeletal development and maintenance together with ephrin ligand (EFN)–receptor (EPH) signaling.

References:

Takada Y, et al. Crosstalk between insulin-like growth factor (IGF) receptor and integrins through direct integrin binding to IGF1. Cytokine Growth Factor Rev, 2017, 34:67-72.
Gallagher EJ, et al. World leaders describe the latest in IGF research. Journal of Molecular Endocrinology, 2018.
Weeks K L, et al. The IGF1-PI3K-Akt Signaling Pathway in Mediating Exercise-Induced Cardiac Hypertrophy and Protection. 2017.
Rhonda D Kineman, et al. Understanding the tissue-specific roles of IGF1IGF1R in regulating metabolism using the CreloxP system1. 2018.
Periyasamy Amutha, et al. Role of Insulin‑like Growth Factor, Insulin‑like Growth Factor Receptors and Insulin‑like Growth Factor‑binding Proteins in Ovarian Cancer. Indian J Med Paediatr Oncol 2017; 38:198-206.
Hakuno F, et al. IGF-I receptor signaling pathways. Journal of Molecular Endocrinology, 2018: JME-17-0311.

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