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The Role of the IGF Axis in Disease, 4th Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 1711

Special Issue Editor


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Guest Editor

Special Issue Information

Dear Colleagues,

This Special Issue continues on from our previous Special Issues, "The Role of the IGF Axis in Disease", “The Role of the IGF Axis in Disease 2.0”, and “The Role of the IGF Axis in Disease, 3nd Edition”.

This research topic aims to highlight the key roles that members of the insulin-like growth factor (IGF) axis (including ligands, IGF-I and -II, IGF binding proteins (IGFBPs1-6) and IGF receptors) play in the risk and development of diseases. The IGF family can affect many physiological systems in the body by modulating cell processes, including proliferation, differentiation, survival, and metabolism. Consequently, they are often dysregulated in many pathological conditions, leading to the development of different strategies to target them.

Dr. Claire M. Perks
Guest Editor

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Keywords

  • IGF axis
  • cancer
  • obesity
  • hallmarks of cancer

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Published Papers (1 paper)

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Research

15 pages, 1708 KiB  
Article
Insulin Receptor Substrate-2 Regulates the Secretion of Growth Factors in Response to Amino Acid Deprivation
by Ayaka Takahashi, Haruka Furuta, Hiroki Nishi, Hiroyasu Kamei, Shin-Ichiro Takahashi and Fumihiko Hakuno
Int. J. Mol. Sci. 2025, 26(2), 841; https://doi.org/10.3390/ijms26020841 - 20 Jan 2025
Viewed by 849
Abstract
Insulin receptor substrates (IRSs) are well-known mediators of the insulin and insulin-like growth factor (IGF)-I signaling pathways. We previously reported that the protein levels of IRS-2, a molecular species of IRS, were upregulated in the livers of rats fed a protein-restricted diet. This [...] Read more.
Insulin receptor substrates (IRSs) are well-known mediators of the insulin and insulin-like growth factor (IGF)-I signaling pathways. We previously reported that the protein levels of IRS-2, a molecular species of IRS, were upregulated in the livers of rats fed a protein-restricted diet. This study aimed to elucidate the physiological role of IRS-2, whose level increases in response to protein restriction in cultured hepatocyte models. Hepatocyte-derived cell lines subjected to amino acid deprivation showed increased IRS2 mRNA and IRS-2 protein levels due to increased IRS2 transcription and translation, respectively. Amino acid deprivation markedly increased vascular endothelial growth factor-D (VEGF-D) secretion. Remarkably, the amino acid deprivation-induced VEGF-D secretion was suppressed by IRS-2 knockdown and enhanced by IRS-2 overexpression. These results suggest that IRS-2 is an intercellular signaling molecule that extracellularly transmits information on amino acid deprivation stress by regulating the secretion of growth factors such as VEGF-D. Moreover, this function of IRS-2 is distinct from its currently accepted function as a mediator of the insulin/IGF-I signaling pathways. This study demonstrates that IRS-2 can modulate protein secretion in an insulin-independent manner and greatly expands our understanding of the role of IRS-2, which is upregulated in response to amino acid deprivation. Full article
(This article belongs to the Special Issue The Role of the IGF Axis in Disease, 4th Edition)
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