The insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and IGFBP proteases are the main regulators of somatic growth and cellular proliferation. IGFs are involved in growth pre-natally and post-natally. Dysregulation of the IGF axis can lead to growth disorders such as growth hormone deficiency and acromegaly. Pre-natally, this dysregulation can lead to IUGR or macrosomia. IGFs also have an important mitogenic action and play a role in tumorigenesis and cancer. These actions are regulated by co-interactions with IGFBPs, especially IGFBP-3. In addition to somatic growth and mitogenic activity, IGFs have hypoglycaemic and insulin sensitizing actions, and their dysregulation is involved in diabetes and its complications. In this chapter, we examine the role of IGFs and IGFBPs in growth, tumorigenesis and diabetes, and discuss treatment modalities for each disease involving the GH-IGF-IGFBP axis, including discussion of current in vitro and in vivo investigations in this field.
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http://dx.doi.org/10.1053/beem.2002.0212 | DOI Listing |
Front Endocrinol (Lausanne)
December 2024
New Mexico State University, Department of Chemistry and Biochemistry, Las Cruces, NM, United States.
Breast cancer is one of the most diagnosed cancers worldwide. The insulin-like growth factor (IGF) system promotes proliferation and survival in breast cancer cells and is regulated by 6 insulin-like growth factor binding proteins (IGFBPs). The IGFBPs sequester IGFs to prolong their half-life and attenuate binding to insulin-like growth factor 1 receptor (IGF1R).
View Article and Find Full Text PDFBiomolecules
November 2024
School of Health and Life Sciences, University of the West of Scotland, Hamilton G72 0LH, UK.
Insulin-like growth factor-binding protein-1 (IGFBP-1) contributes to the regulation of IGFs for metabolism and growth and has IGF-independent actions. IGFBP-1 in the circulation is derived from the liver, where it is inhibited by insulin and stimulated by multiple factors, including proinflammatory cytokines. IGFBP-1 levels are influenced by sex and age, which also determine cardiometabolic risk and patterns of disease presentation.
View Article and Find Full Text PDFPathophysiology
November 2024
Department of Endocrinology, Hippokration Hospital, 11527 Athens, Greece.
Critical illness (CI) triggers complex disruptions in the growth hormone (GH)/insulin-like growth factor (IGF) axis, significantly affecting the dynamics of insulin-like growth-factor-binding proteins (IGFBPs). Among these, IGFBP-2 shows a sustained elevation during CI, which inversely correlates with serum levels of IGF-1, IGFBP-3, and the acid-labile subunit (ALS). Although IGFBP-2 does not directly interact with ALS, it may influence the availability of IGFs by competing with other IGFBPs for binding to IGF-1 and IGF-2.
View Article and Find Full Text PDFPoult Sci
December 2024
College of Animal Science and Technology, Shandong Agricultural University, Taian 271017, China; Shandong Provincial Key laboratory for Livestock Germplasm Innovation & Utilization, Shandong Agricultural University, Taian 271017, China. Electronic address:
Int Immunopharmacol
December 2024
Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. Electronic address:
IGFALS forms stable ternary complexes with insulin-like growth factors (IGF1 and IGF2) and IGF-binding proteins (IGFBP3 and IGFBP5), which prolong the half-lives of IGFs. Through immunohistochemical analysis of 90 pairs of clinical samples and bioinformatics analysis, we observed downregulation of IGFALS in hepatocellular carcinoma tissues, which was associated with poor patient prognosis. This prompted us to explore the specific molecular mechanism of action of IGFALS in the inhibition of hepatocellular carcinoma (HCC), which could be a potential new target for the treatment of HCC.
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