Insulin Receptor Substrate Proteins

A structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. The proteins share in common an N-terminal PHOSPHOLIPID-binding domain, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. Upon tyrosine phosphorylation insulin receptor substrate proteins interact with specific SH2 DOMAIN-containing proteins that are involved in insulin receptor signaling.
Also Known As:
IRS Signaling Adaptor Proteins; Insulin Receptor Substrate-1; Insulin Receptor Substrate-1 Protein; Insulin Receptor Substrate-2; Insulin Receptor Substrate-2 Protein; Insulin Receptor Substrate-3; Insulin Receptor Substrate-3 Protein; Insulin Receptor Substrate-4; Insulin Receptor Substrate-4 Protein; Insulin Receptor Substrate 1; Insulin Receptor Substrate 1 Protein; Insulin Receptor Substrate 2; Insulin Receptor Substrate 2 Protein; Insulin Receptor Substrate 3; Insulin Receptor Substrate 3 Protein; Insulin Receptor Substrate 4; Insulin Receptor Substrate 4 Protein
Networked: 588 relevant articles (13 outcomes, 52 trials/studies)

Relationship Network

Bio-Agent Context: Research Results


1. Kadowaki, Takashi: 11 articles (12/2011 - 11/2002)
2. Terauchi, Yasuo: 10 articles (05/2014 - 11/2002)
3. White, Morris F: 10 articles (07/2013 - 01/2002)
4. Shaw, Leslie M: 6 articles (12/2011 - 11/2004)
5. Tobe, Kazuyuki: 6 articles (06/2006 - 06/2003)
6. Suzuki, Ryo: 6 articles (06/2006 - 06/2003)
7. Shulman, Gerald I: 5 articles (04/2011 - 12/2002)
8. Baserga, Renato: 5 articles (08/2009 - 03/2007)
9. Kubota, Naoto: 5 articles (03/2009 - 06/2003)
10. Kadowaki, T: 5 articles (11/2008 - 01/2000)

Related Diseases

1. Insulin Resistance
2. Corneal Neovascularization
3. Glucose Intolerance
10/01/2013 - "Neuronal overexpression of insulin receptor substrate 2 leads to increased fat mass, insulin resistance, and glucose intolerance during aging."
05/01/2015 - "This study aimed to measure the hepatic expression of insulin receptor substrate-2 (IRS-2) and glucose transporter-2 (GLUT-2) in type 2 diabetic rats post-DJE, and to investigate their roles in improved hepatic insulin resistance and glucose intolerance. "
07/01/2003 - "In order to understand the role of the insulin receptor substrate-2 (IRS2) gene (chromosome region: 13q34) in obesity, a complex disorder associated with insulin resistance and glucose intolerance, we determined single nucleotide polymorphims (SNPs) and complex haplotypes in women with morbid obesity and a body mass index (BMI) of 41+/-0.8 kg/m2 ( n=99) compared with controls having a BMI of 23.8+/-0.1 kg/m2 ( n=92). "
04/01/2007 - "At the same time, the HS-induced glucose intolerance, impaired postprandial glycemic control, and decrease in muscle and liver insulin-induced activation of insulin receptor substrate 1 and Akt were prevented by increasing the level of dietary cysteine, a major original finding. "
12/01/2010 - "Remarkably, disruption of Alox15 attenuated glucose intolerance and high-fat diet-induced insulin resistance, up-regulated insulin receptor substrate-2, and exerted opposite effects on hepatic c-Jun amino-terminal kinase and adenosine monophosphate-activated protein kinase phosphorylation, known negative and positive regulators of insulin signaling, respectively. "
4. Muscular Atrophy (Muscle Atrophy)
5. Inflammation
04/01/2014 - "The antiangiogenic insulin receptor substrate-1 antisense oligonucleotide aganirsen impairs AU-rich mRNA stability by reducing 14-3-3β-tristetraprolin protein complex, reducing inflammation and psoriatic lesion size in patients."
03/01/2010 - "In summary, we show that, in a rodent model of T2DM, voluntary exercise decreases circulating markers of inflammation and oxidative stress and lowers hepatic JNK activation and Ser(307)-phosphorylated insulin receptor substrate-1. "
07/01/2009 - "The 8-OhdG immunolocalization in liver tissues of the group 4 obviously decreased compared with those of groups 2 and 3. For Western blotting, the expressions of insulin receptor substrate-1 (IRS-1) and phosphorylated IRS-1 (pIRS-1) in liver tissues of group 4 increased compared with those of groups 2 and 3. On the other hand, the expressions of pAkt, pIKKbeta and pNF-kappaB decreased compared with those of groups 2 and 3. From these results, EGCG reduces inflammation, insulin resistance and oxidative stress, and suppresses liver injury in nSREBP-1c transgenic mice."
09/01/2014 - "Nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNFα) and the level of inhibitory phosphorylation of insulin receptor substrate-1 (IRS-1) on Ser(307) were analyzed as markers of hepatic inflammation. "
12/01/2012 - "Importantly, treatment of adipocytes with the supernatant of activated Y1-deficient macrophages causes insulin resistance, as demonstrated by decreased insulin-induced phosphorylation of the insulin receptor and Akt as well as decreased expression of insulin receptor substrate 1. Thus, Y1 signaling in hematopoietic-derived cells such as macrophages is critical for the control of inflammation and insulin resistance in obesity."

Related Drugs and Biologics

1. Phosphotransferases (Kinase)
2. Glucose (Dextrose)
3. Interleukin-6 (Interleukin 6)
4. Insulin (Novolin)
5. Tumor Necrosis Factor-alpha (Tumor Necrosis Factor)
6. Insulin Receptor Substrate Proteins
7. Leptin
8. Insulin Receptor
9. Ophthalmic Solutions (Eye Drops)
10. Facilitative Glucose Transport Proteins (Glucose Transporter)

Related Therapies and Procedures

1. Resistance Training
2. Injections
3. Reducing Diet
4. Gastric Bypass (Roux-en-Y Gastric Bypass)
5. Heterologous Transplantation (Xenotransplantation)