IGF-1: A Drug Target and Biomarker (G3479)

NCBI ID: G3479

IGF1

IGF-1: A Drug Target and Biomarker

IGF-1, also known as insulin-like growth factor 1, plays a crucial role in various biological processes. It acts through the insulin/IGF-1 receptor and triggers a kinase cascade that influences gene transcription and cell functions. In C. elegans, the DAF-2/DAF-16 pathway regulates lifespan and dauer development, with IGF-1 inhibiting DAF-16/FOXO's nuclear translocation and gene transcription. In mice, IGF-1 enhances the synthesis and release of GnRH, which stimulates the production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). IGF-1 also regulates the expression of TXNIP, a protein involved in cell survival and homeostasis, through downregulation of oxidative and glucose stress-induced TXNIP upregulation. Additionally, abnormal insulin/IGF-1 signaling and tau phosphorylation have been implicated in neurodegenerative diseases such as Parkinson's and Alzheimer's. The balance between GH and IGF-1, regulated through a negative feedback loop involving Klotho, affects inflammation, insulin resistance, and atherosclerosis.

Overall, IGF-1 has diverse effects on cell function, lifespan regulation, reproduction, cell survival, and disease processes.
Based on the provided context information, multiple viewpoints on IGF1 can be summarized as follows:

IGF1 signaling and SNHG7 regulate the expression of a similar gene set, and both are necessary for proliferation. IGF1 signaling decreases SNHG7 expression, while SNHG7 enhances the expression of IGF1 signaling molecules. This creates a fine-tuning feedback mechanism that tightly regulates the proliferation response.

Laminar shear stress induces the release of stored neutrophil elastase via ATP/P2Y2 signaling. Elastase, in turn, degrades fibronectin and activates alphavbeta3 integrin, facilitating IGF-1/IGF1R signaling. This pathway also plays a role in the secretion of FGF-2.

The GH-IGF-I axis involves the interaction of GH with cell surface dimeric GH receptors, leading to the activation of signaling cascades. This ultimately regulates the production of circulating IGF-I, IGFBP-3, and ALS. Mutations in various components of this axis can result in GHI and IGF deficiency, IGF bioavailability issue, or IGF resistance.

Low serum IGF-I levels can lead to metabolic changes, such as reduced peripheral glucose and lipid uptake, increased liver glucose production, and elevated circulating glucose and free fatty acid levels.

In hiPSC-CMs (human induced pluripotent stem cell-derived cardiomyocytes), receptor tyrosine kinases VEGFR2, PDGFRalpha, INSR, and IGF1R are upstream of pro-survival signaling pathways. Blockade of VEGFR2/PDGFR phosphorylation by TKIs (tyrosine kinase inhibitors) can lead to a compensatory upregulation of INSR and IGF1R signaling to enhance cardiomyocyte survival. This compensatory effect may be further augmented by introducing exogenous insulin and IGF1 ligands.

By combining similar viewpoints, we can summarize the key findings as follows:

IGF1 signaling and SNHG7 play important roles in regulating gene expression and proliferation. Neutrophil elastase secretion and its interaction with alphavbeta3 integrin contribute to IGF-1/IGF1R signaling and FGF-2 secretion. The GH-IGF-I axis is involved in the regulation of IGF-I production and mutations in this pathway can result in various conditions affecting IGF function. Low serum IGF-I levels can lead to metabolic changes. In hiPSC-CMs, blockade of VEGFR2/PDGFR signaling can result in compensatory upregulation of INSR and IGF1R signaling, potentially promoting cardiomyocyte survival.

Protein Name: Insulin Like Growth Factor 1

Functions: The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation (PubMed:21076856, PubMed:24132240). Ca(2+)-dependent exocytosis of IGF1 is required for sensory perception of smell in the olfactory bulb (By similarity). Acts as a ligand for IGF1R. Binds to the alpha subunit of IGF1R, leading to the activation of the intrinsic tyrosine kinase activity which autophosphorylates tyrosine residues in the beta subunit thus initiatiating a cascade of down-stream signaling events leading to activation of the PI3K-AKT/PKB and the Ras-MAPK pathways. Binds to integrins ITGAV:ITGB3 and ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and IGFR1 are essential for IGF1 signaling. Induces the phosphorylation and activation of IGFR1, MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:19578119, PubMed:22351760, PubMed:23696648, PubMed:23243309)

The "IGF1 Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about IGF1 comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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