scholarly journals Insulin-like growth factor axis during embryonic development

Reproduction ◽  
2001 ◽  
pp. 31-39 ◽  
Author(s):  
GJ Allan ◽  
DJ Flint ◽  
K Patel
Keyword(s):  
Growth Factor ◽  
Expression Patterns ◽  
Limb Bud ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Igf System ◽  
Type I Igf Receptor ◽  
Igf Binding ◽  
Mrna And Protein Expression

The insulin-like growth factor (IGF) axis has been studied extensively in the developing vertebrate embryo. Knockout experiments have demonstrated that both IGF-I and -II are required for normal development in the mouse embryo, and mRNA and protein expression patterns for both growth factors, together with those for the type I IGF receptor and the six IGF-binding proteins, have been analysed in embryos from different species. Although the unique temporal and spatial expression patterns of these genes indicates important roles for the IGF axis during organ and whole animal development, the variation and complexity of expression makes these roles difficult to unravel. However, one possible mechanism unifying the IGF system in development is programmed cell death (apoptosis), which has been shown to be important in sculpting embryonic tissues, and, in particular, the developing limb bud. In addition, the very early onset of expression of various IGF family members in chicken embryos further emphasizes the fundamental importance of this system in development. This article reviews the work that has been carried out in this area in the context of current understanding of the IGF system.

Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities

2000 ◽  
Vol 278 (6) ◽  
pp. E967-E976 ◽  
Author(s):  
Robert C. Baxter
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Specific Cell ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Serine Kinase ◽  
Homologous Proteins ◽  
Igf Binding Proteins ◽  
Type I Igf Receptor ◽  
Igf Binding

The insulin-like growth factor (IGF)-binding proteins (IGFBPs) are a family of six homologous proteins with high binding affinity for IGF-I and IGF-II. Information from NMR and mutagenesis studies is advancing knowledge of the key residues involved in these interactions. IGF binding may be modulated by IGFBP modifications, such as phosphorylation and proteolysis, and by cell or matrix association of the IGFBPs. All six IGFBPs have been shown to inhibit IGF action, but stimulatory effects have also been established for IGFBP-1, -3, and -5. These generally involve a decrease in IGFBP affinity and may require cell association of the IGFBP, but precise mechanisms are unknown. The same three IGFBPs have well established effects that are independent of type I IGF receptor signaling. IGFBP-1 exerts these effects by signaling through α5β1-integrin, whereas IGFBP-3 and -5 may have specific cell-surface receptors with serine kinase activity. The regulation of cell sensitivity to inhibitory IGFBP signaling may play a role in the growth control of malignant cells.

Effects of Maternal Diabetes on Fetal Expression of Insulin-Like Growth Factor and Insulin-Like Growth Factor Binding Protein MRNAs in the Rat

1995 ◽  
Vol 147 (2) ◽  
pp. R5-R8 ◽  
Author(s):  
Randal D. Streck ◽  
Veeraramani S. Rajaratnam ◽  
Renata B. Fishman ◽  
Peggy J. Webb
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Fetal Growth ◽  
Fetal Liver ◽  
Expression Patterns ◽  
Maternal Diabetes ◽  
Limb Bud ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Increased Risk

ABSTRACT Matemal diabetes is associated in humans and rats with an increased risk for fetal growth abnormalities and malformations. Therefore, the effect of maternal diabetes on expression of genes that regulate fetal growth and differentiation is of considerable interest. Developmental growth is regulated in part by the expression and availability of insulin-like growth factors (IGFs). Postnatal expression of a subset of the IGFs and IGF binding proteins (IGFBPs) has been demonstrated to be regulated in response to diabetes and other metabolic conditions. We used in situ hybridization to analyze the effect of maternal diabetes, induced by streptozotocin (STZ) prior to mating, upon prenatal rat IGF and IGFBP mRNA expression. At gestational day (GD) 14, the most striking effect of maternal diabetes on fetal IGF/IGFBP gene expression was a marked increase in the abundance of IGFBP-1 mRNA within the liver primordia of fetuses isolated from diabetic dams compared to age-matched controls. This upregulation cannot be entirely due to the approximately one-half-day delay in fetal development (based on limb bud staging) associated with maternal diabetes, as there was no gross difference in the level of IGFBP-1 mRNA between GD13 and GD14 control fetal livers. In contrast, the fetal mRNA expression patterns of IGF-I, IGF-II and IGFBP-2, -3, -4, -5 and -6 were not grossly altered by maternal diabetes. These data are consistent with the hypothesis that IGFBP-1 produced within the fetal liver and secreted into fetal circulation may play a role in regulating rat fetal growth.

scholarly journals Molecular Signatures of the Insulin-like Growth Factor 1-mediated Epithelial-Mesenchymal Transition in Breast, Lung and Gastric Cancers

2018 ◽  
Vol 19 (8) ◽  
pp. 2411 ◽  
Author(s):  
Armando Cevenini ◽  
Stefania Orrù ◽  
Annamaria Mancini ◽  
Andreina Alfieri ◽  
Pasqualina Buono ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Molecular Signatures ◽  
Insulin Like Growth Factor ◽  
Cancer Proliferation ◽  
Igf Binding Proteins ◽  
Mesenchymal Transition ◽  
Gastric Cancers ◽  
Igf System ◽  
Igf Binding

The insulin-like growth factor (IGF) system, which is constituted by the IGF-1 and IGF-2 peptide hormones, their corresponding receptors and several IGF binding proteins, is involved in physiological and pathophysiological processes. The IGF system promotes cancer proliferation/survival and its signaling induces the epithelial-mesenchymal transition (EMT) phenotype, which contributes to the migration, invasiveness, and metastasis of epithelial tumors. These cancers share two major IGF-1R signaling transduction pathways, PI3K/AKT and RAS/MEK/ERK. However, as far as we could review at this time, each type of cancer cell undergoes EMT through tumor-specific routes. Here, we review the tumor-specific molecular signatures of IGF-1-mediated EMT in breast, lung, and gastric cancers.

Insulin-like growth factor-binding protein-6 and cancer

2012 ◽  
Vol 124 (4) ◽  
pp. 215-229 ◽  
Author(s):  
Leon A. Bach ◽  
Ping Fu ◽  
Zhiyong Yang
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Cancer Therapeutics ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Igf System ◽  
Binding Preference ◽  
Inhibition Of Angiogenesis ◽  
Igf Binding ◽  
Independent Effects

The IGF (insulin-like growth factor) system is essential for physiological growth and it is also implicated in a number of diseases including cancer. IGF activity is modulated by a family of high-affinity IGF-binding proteins, and IGFBP-6 is distinctive because of its marked binding preference for IGF-II over IGF-I. A principal role for IGFBP-6 is inhibition of IGF-II actions, but recent studies have indicated that IGFBP-6 also has IGF-independent effects, including inhibition of angiogenesis and promotion of cancer cell migration. The present review briefly summarizes the IGF system in physiology and disease before focusing on recent studies on the regulation and actions of IGFBP-6, and its potential roles in cancer cells. Given the widespread interest in IGF inhibition in cancer therapeutics, increasing our understanding of the mechanisms underlying the actions of the IGF ligands, receptors and binding proteins, including IGFBP-6, will enhance our ability to develop optimal treatments that can be targeted to the most appropriate patients.

The insulin-like growth factor system in the circulation of patients with viral infections

2004 ◽  
Vol 42 (10) ◽  
Author(s):  
Ivona Baričević ◽  
Olgica Nedić ◽  
Judith Anna Nikolić ◽  
Jasminka Nedeljković
Keyword(s):  
Growth Factor ◽  
Viral Infections ◽  
Serum Cortisol ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Ligand Affinity ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Simplex Virus

AbstractThe insulin-like growth factor (IGF) system was examined in the circulation of patients with viral infections (herpes simplex virus, HSV; cytomegalovirus, CMV; rotavirus, RV and adenovirus, AV). The serum concentrations of IGF-I, IGF-II and cortisol were measured by radioimmunoassay, while IGF-binding proteins (IGFBPs) were characterised by ligand-affinity blotting. Although both IGF-I and IGF-II concentrations were significantly lower in patients with viral infections (p < 0.05) than in healthy persons, the IGF-II/IGF-I ratio was increased (p < 0.05). No correlation between the concentration of IGF-I and IGF-II and the intensity of the antibody response to infection was observed. Ligand-affinity blotting demonstrated decreased amounts of IGFBP-3 (patients with HSV, CMV, AV and some patients with RV), increased IGFBP-2 (some patients with HSV and RV) and IGFBP-1 (patients with RV). Serum cortisol was significantly elevated (p < 0.05) in patients infected with HSV, CMV and RV. The alterations observed can be interpreted as induction of the hypothalamic-pituitary-adrenal axis and suppression of the growth hormone (GH)/IGF axis under the influence of viral infection.

scholarly journals Insulin-like Growth Factor 1 Signaling in Mammalian Hearing

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1553
Author(s):  
Ángela García-Mato ◽  
Blanca Cervantes ◽  
Silvia Murillo-Cuesta ◽  
Lourdes Rodríguez-de la Rosa ◽  
Isabel Varela-Nieto
Keyword(s):  
Hearing Loss ◽  
Growth Factor ◽  
Biological Effects ◽  
Expression Patterns ◽  
Peptide Hormone ◽  
Tyrosine Kinase Receptor ◽  
Insulin Like Growth Factor ◽  
Mammalian Development ◽  
Igf Binding Proteins ◽  
Igf System

Insulin-like growth factor 1 (IGF-1) is a peptide hormone belonging to the insulin family of proteins. Almost all of the biological effects of IGF-1 are mediated through binding to its high-affinity tyrosine kinase receptor, (IGF1R), a transmembrane receptor belonging to the insulin receptor family. Factors, receptors and IGF-binding proteins form the IGF system, which has multiple roles in mammalian development, adult tissue homeostasis, and aging. Consequently, mutations in genes of the IGF system, including downstream intracellular targets, underlie multiple common pathologies and are associated with multiple rare human diseases. Here we review the contribution of the IGF system to our understanding of the molecular and genetic basis of human hearing loss by describing, (i) the expression patterns of the IGF system in the mammalian inner ear; (ii) downstream signaling of IGF-1 in the hearing organ; (iii) mouse mutations in the IGF system, including upstream regulators and downstream targets of IGF-1 that inform cochlear pathophysiology; and (iv) human mutations in these genes causing hearing loss.

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