IRS1

(redirected from insulin receptor substrate 1)

IRS1

A gene on chromosome 2q36 that encodes a protein phosphorylated by insulin receptor tyrosine kinase; it is thought to mediate the effects of insulin, insulin-like growth factor 1 and other cytokines by acting as a molecular adaptor between various receptor tyrosine kinases and downstream effectors.
 
Molecular pathology
IRS1 mutations are associated with type-2 diabetes and insulin resistance.
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In a study on lactational programming and insulin signalling, mice were overfed during lactation and displayed increased insulin receptor-[beta] (IR-[beta]) content, reduced IR-3 phosphorylation, unaltered insulin receptor substrate 1 (IRS1) content but with decreased phosphorylation, decreased Akt1/protein kinase B (PKB) (Akt1) content, and impaired insulin signalling as there was a decrease in Akt1 phosphorylation as well as a decrease in phosphoinositide 3-kinase-insulin receptor substrate 1 (PI3K-IRS1) interaction [53].
Normally, insulin activates several cascades of intracellular signalling pathways, which begins with phosphorylation of insulin receptor substrate 1 & 2 (IRS-1 & 2) and is followed by activation of phosphotidylinositide 3 kinase (PI3-K) and protein kinase B (AKT).
In preeclampsia-suffering women, an abnormal intracellular amount of DCIns within the placenta promotes a specific phosphorylation of insulin receptor substrate 1 (IRS-1) on [serine.sup.312] and leads to inhibition of the PI3K/Akt pathway [92].
AMPK further mediates important downstream effects of adiponectin, including enhanced insulin sensitivity in part through serine phosphorylation of insulin receptor substrate 1 (IRS-1) [40].
We have previously reported TNF[alpha] increased insulin receptor substrate 1 [(IRS-1).sup.Ser307] phosphorylation in REC, thus blocking insulin signal transduction [12].
Obesity changes the secretion of adipose tissue inflammatory cytokines, which modulate insulin signaling, so we analyzed the insulin signaling gene expression including insulin receptor (IR), insulin receptor substrate 1 (IRS-1), and IRS-2 in liver tissue.
It has been shown that genotype 3a affects the insulin signalling pathway through down-regulation of peroxisome proliferator-activated receptor.10 It has been shown that there is increased production of suppressor of cytokine signalling 7 (SOCS 7) in genotype 3, resulting in diminished insulin receptor substrate 1 (IRS-1) and thus leading to IR.11 IRS-1 is down-regulated by mammalian target of Rapamycin (mTOR) in genotype 1b which shows a connection between HCV-1b infection and IR at the early stage of liver disease.12 IR and development of type 2 diabetes mellitus (T2DM) has been shown to be associated with progression of liver fibrosis.13 So, it is not usually encountered in early years of HCV infection.
These kinases are activated in high-fat diet-induced or saturated fatty acid-induced insulin resistance and have been reported to catalyze the phosphorylation of serine residues in insulin receptor substrate 1 (IRS-1), leading to a reduction in the phosphorylation of tyrosine residues of IRS-1 and in the activity of downstream signaling pathways activated by insulin (6,7).
Insulin stimulation of phosphatidylinositol 3-kinase activity and association with insulin receptor substrate 1 in liver and muscle of the intact rat.
One of the few T2D loci associated with insulin resistance (IR) encodes insulin receptor substrate 1 (IRS1), a key protein central to the insulin signaling pathway (3).
Bataille et al., "Serine phosphorylation of insulin receptor substrate 1 by inhibitor kB kinase complex," Journal of Biological Chemistry, vol.
One possibility is the down regulation of insulin receptor substrate 1 (IRS1 ) expression (Turnbow et al.

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