Last update 01 Nov 2024

IGF-1R x IRS-1 x IRS2

Last update 01 Nov 2024

Basic Info

Related Targets

IGF-1RIRS-1IRS2

Drugs associated with IGF-1R x IRS-1 x IRS2

NT-157

Target

IGF-1R x IRS-1 x IRS2

Mechanism

IGF-1R antagonists [+2]

Active Org.-

Originator Org.

The Hebrew University of Jerusalem

Active Indication-

Inactive Indication

Prostatic Cancer

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with IGF-1R x IRS-1 x IRS2

100 Translational Medicine associated with IGF-1R x IRS-1 x IRS2

0 Patents (Medical) associated with IGF-1R x IRS-1 x IRS2

147

Literatures (Medical) associated with IGF-1R x IRS-1 x IRS2

01 Jan 2023·Frontiers in oncology

A systematic review and meta-analysis for the association of the insulin-like growth factor1 pathway genetic polymorphisms with colorectal cancer susceptibility.

Review

Author: Piroozkhah, Moein ; Sadeghi, Amir ; Shojaee, Sajad ; Cheraghpour, Makan ; Tierling, Sascha ; Ketabi Moghadam, Pardis ; Khazdouz, Maryam ; Asadzadeh Aghdaei, Hamid ; Askari, Masomeh ; Fatemi, Nayeralsadat ; Nazemalhosseini-Mojarad, Ehsan

BackgroundThe receptors, ligands, and associated proteins of the insulin-like growth factor (IGF) family are involved in cancer development. The IGF1 receptor and its accompanying signaling cascade are a crucial growth-regulatory mechanism that plays an important role in colorectal cancer (CRC) proliferation and differentiation. IRS1 (Insulin receptor substrate-1), a major substrate for the IGF1R, is involved in cell growth and promotes tumorigenesis. There are shreds of evidence from prior research suggesting that IGF system polymorphisms may influence susceptibility to CRC. However, the findings in this area were contradictory. Accordingly, we carried out a systematic literature search to identify all case-control, cross-sectional, and cohort studies on the association between various polymorphisms across four IGF1 pathway genes (IGF1, IGF1R, IRS1, and IRS2) and the risk of CRC.MethodsWe performed a comprehensive search strategy in PubMed, Scopus, and Web of Science databases for articles available until Aug 30, 2022. A total of 26 eligible studies with IGF1/IGF1R, IRS1 and IRS2 polymorphisms; met the inclusion criteria. All case-control studies for IGF1 rs6214C>T, IRS1 rs1801278G>A, and IRS2 rs1805097G>A comprising 22,084 cases and 29,212 controls were included in the current meta-analysis. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate relationships between the polymorphisms and CRC susceptibility. All statistical analyses were performed using STATA software version 14.0.ResultsThe meta-analysis of available data for rs6214C>T, rs1801278G>A, and rs1805097G>A showed a significant association between these polymorphisms and an increased CRC risk in some of the comparisons studied (rs6214C>T, pooled OR for CC = 0.43, 95% CI 0.21- 0.87, P = 0.019; rs1801278G>A, OR for GA = 0.74, 95% CI 0.58-0.94, P = 0.016; rs1805097G>A, OR for GA = 0.83, 95% CI 0.71-0.96, P = 0.013). Nevertheless, the meta-analysis did not include other genetic variations in IGF1, IGF1R, IRS1, and IRS2 due to heterogeneity and limited sample size.ConclusionsThis systematic review and meta-analysis provide evidence that genetic variants in IGF1 rs6214C>T, IRS1 rs1801278G>A, and IRS2 rs1805097G>A are associated with an increased risk of CRC. These findings may contribute to a better understanding of the complex genetic mechanisms involved in CRC development and could inform future research on prevention and treatment strategies for this disease.

21 Oct 2022·Genetics Research

Upregulation of Klotho Aggravates Insulin Resistance in Gestational Diabetes Mellitus Trophoblast Cells

Article

Author: Zhao, Weihua ; Lin, Li ; Wang, Xinyu ; Chen, Yaxuan

Objective. Insulin resistance (IR) plays a key role in gestational diabetes mellitus (GDM) pathogenesis. The antiaging protein klotho has been proven to be closely related to IR. The purpose of this study was to investigate the effect of klotho on IR in GDM trophoblast cells. Methods. The GDM cell model of HTR-8/SVneo cells was induced by high glucose (HG). Plasmid transfection was used to mediate the overexpression or silencing of klotho. The effects of klotho on cell viability, IR, and the IGF-1/PI3K pathways were observed by RT-qPCR, western blot, Cell Counting Kit-8 detection, glucose uptake assay, and immunofluorescence detection. Results. Klotho expression was up-regulated in HG-induced cells. Overexpression of klotho could reduce the cell viability, insulin signaling molecules (INSR-α, INSR-β, IRS1, IRS2, and GLUT4), and glucose uptake in HTR-8/SVneo cells of the HG group. In addition, the overexpression of klotho inhibited the levels of IGF-1, IGF-1R/p-IGF-1R, and the phosphorylation and activation of the signal transduction molecules PI3K/Akt/mTOR. On the contrary, klotho deletions could reverse these changes of HTR-8/SVneo cells induced by HG. Conclusion. In a word, the results of this study showed that the regulation of klotho played an important role in the IR of trophoblast cells induced by HG, which was mediated at least in part by the IGF-1/PI3K/Akt/mTOR pathway.

01 Jan 2022·Molecular and Cellular NeuroscienceQ2 · MEDICINE

IRS1 expression in hippocampus is age-dependent and is required for mature spine maintenance and neuritogenesis

Q2 · MEDICINE

Article

Author: Beltrán-Bretones, Maria Teresa ; ElMlili, Nisrin ; García-Díaz, Cristina ; Sánchez-Pérez, Ana María ; Sánchez-Sarasúa, Sandra ; Meseguer-Beltrán, María

Insulin and insulin-like growth factor type I (IGF-1) play prominent roles in brain activity throughout the lifespan. Insulin/IGF1 signaling starts with the activation of the intracellular insulin receptor substrates (IRS). In this work, we performed a comparative study of IRS1 and IRS2, together with the IGF1 (IGF1R) and insulin (IR) receptor expression in the hippocampus and prefrontal cortex during development. We found that IRS1 and IRS2 expression is prominent during development and declines in the aged hippocampus, contrary to IR, which increases in adulthood and aging. In contrast, IGF1R expression is unaffected by age. Expression patterns are similar in the prefrontal cortex. Neurite development occurs postnatally in the rodent hippocampus and cortex, and it declines in the mature and aged brain and is influenced by trophic factors. In our previous work, we demonstrated that knockdown of IRS1 by shRNA impairs learning and reduces synaptic plasticity in a rat model, as measured by synaptophysin puncta in axons. In this study, we report that shIRS1 alters spine maturation in adult hilar hippocampal neurons. Lastly, to understand the role of IRS1 in neuronal neurite tree, we transfect shIRS1 into primary neuronal cultures and observed that shIRS1 reduced neurite branching and neurite length. Our results demonstrate that IRS1/2 and insulin/IGF1 receptors display different age-dependent expression profiles and that IRS1 is required for spine maturation, demonstrating a novel role for IRS1 in synaptic plasticity.

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