[7] Together with IRS2, IRS3 (pseudogene) and IRS4, it is homologous to the Drosophila protein chico, whose disruption extends the median lifespan of flies up to 48%.

[8] Similarly, Irs1 mutant mice experience moderate life extension and delayed age-related pathologies.

Tyrosine phosphorylation of IRS-1 by insulin receptor (IR) introduces multiple binding sites for proteins bearing SH2 homology domain, such as PI3K, Grb-2/Sos complex and SHP2.

It has been shown that TNFα causes insulin resistance and multi-site S/T phosphorylation, which results in block of interaction between IRS-1 and juxtamembrane domain peptide, thus converting IRS-1 into an inactive state.

During insulin resistance induced by hyperglycemia, glucose accumulates in tissues as its hexosamine metabolite UDP-GlcNAc.

Reduced expression of IRS-1 in Apc (min/+) mutated mice shows increased irradiation-induced apoptosis in crypt.

Neutrophil elastase is shown to degrade IRS-1 by gaining access to endosomal compartment of carcinoma cell.

Ablation of IRS-1 alters downstream signalling through phosphatidylinositol-3 kinase (PI3K), causing an increased interaction of it with platelet-derived growth factor receptor (PDGFR).

During progression of preneoplastic foci into hepatocellular carcinomas expression of IRS-1 gradually decreases, which is characterises a metabolic shift heading towards malignant neoplastic phenotype.

[41] Transgenic mice, co-expressing IRS-1 and hepatitis Bx (HBx) protein, demonstrate higher rate of hepatocellular displasia that results in HCC development.

When treated with insulin, ectopic expression of PTEN in MCF-7 suppresses IRS-1/Grb-2/Sos complex formation due to differential phosphorylation of IRS-1.

Tamoxifen (TAM) inhibits IRS-1 function, therefore suppressing IRS-1/PI3K signalling cascade in estrogen receptor positive (ER+) MCF-7 cell line.

[47] Estradiol enhances expression of IRS-1 and activity of ERK1/2 and PI3K/Akt pathways in MCF-7 and CHO cells transfected with mouse IRS-1 promoter.

Estradiol acts directly on IRS-1 regulatory sequences and positively regulates IRS-1 mRNA production.

Basically, IRS-2 has a positive impact on metastasis of breast cancer whereas a stronger metastatic potential is observed when IRS-1 is down-regulated.

[citation needed] IRS-1 is strongly expressed in ductal carcinoma in situ, when IRS-2 is elevated in invasive tumors.

Increased IRS-1 makes MCF-7 cells susceptible to specific chemotherapeutic agents, such as taxol, etoposide, and vincristine.

Therefore, IRS-1 can be a good pointer of specific drug therapies effectiveness for breast cancer treatment.