Interaction of irs proteins insulin receptor substrate proteins. Medical search. Frequent questions

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. (wikipedia.org)
This phosphorylation is absent in tissues lacking IRS-1. (wikipedia.org)
Tyrosine phosphorylation of the insulin receptors or IGF-1 receptors, upon extracellular ligand binding, induces the cytoplasmic binding of IRS-1 to these receptors, through its PTB domains. (wikipedia.org)
An alternative multi-site phosphorylation of Serine/Threonine in IRS-1 regulates insulin signaling positively and negatively. (wikipedia.org)
C-terminal region contains most of the phosphorylation sites of the protein. (wikipedia.org)
The C-terminal tail is not structured, therefore the mechanisms of regulation of IRS-1 by phosphorylation still remain unclear. (wikipedia.org)
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. (wikipedia.org)
Different Serine phosphorylation of IRS-1, caused by various molecules, such as fatty acids, TNFα and AMPK, has different effects on the protein, but most of these effects include cellular re-localization, conformational and steric changes. (wikipedia.org)
These processes lead to decrease in Tyrosine phosphorylation by insulin receptors and diminished PI3K recruitment. (wikipedia.org)
SOCS proteins act by binding to IR and by interfering with IR phosphorylation of IRS-1, therefore attenuating insulin signaling. (wikipedia.org)
They can also bind to JAK, causing a subsequent decrease in IRS-1 tyrosine phosphorylation. (wikipedia.org)
IRS-1 can undergo this modification, which results in its phosphorylation and functional suppression. (wikipedia.org)
In addition to subcellular location and protein-protein interactions, several phosphorylation and dephosphorylation sites also modulate eNOS activity ( 9 ). (diabetesjournals.org)
It is worth noting that we have found the key upstream target of DOX-induced HF, PTP1B, which inhibits the expression of HIF-1α by inhibiting the phosphorylation of IRS, leading to disorders of fatty acid metabolism and glycolysis, which together with the decrease of Nrf2, SOD, Cytc, and AK4 proteins lead to oxidative stress. (frontiersin.org)
Cav1 and its phosphorylation can impact on the domain recruitment of signalling protein partners and consequently contribute to the trafficking of signalling proteins to and from the plasma membrane. (diff.org)
Ser80 phosphorylation serves to convert Cav1 to a soluble secreted protein. (diff.org)
This was associated with DIM‐enhanced phosphorylation of the signaling intermediates Akt, insulin receptor substrate‐1, and insulin receptor early in differentiation. (researchgate.net)
An insulin-sensitive serine/threonine kinase casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. (thermofisher.com)
Thr 502 is identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1, and Ser 99 is an additional phosphorylation site catalyzed by casein kinase II. (thermofisher.com)
Thus, casein kinase II-catalyzed phosphorylation of IRS-1 may be a component of the intracellular insulin signaling cascade. (thermofisher.com)
Akt activation leads to the phosphorylation and inactivation of various downstream targets, including glycogen synthase kinase 3 (GSK3), which regulates glycogen synthesis, and the mammalian target of rapamycin (mTOR), which controls protein synthesis and cell growth. (ebiwinner.com)
Subcellular localization of IRS-1 and phosphorylation levels of mitogen-activated protein kinase and Akt1 were also analyzed.IGF-IR was differentially expressed across histologic subtypes (P = 0.04), with highest levels observed in squamous cell tumors. (omicsdi.org)
Among PTMs, protein phosphorylation is the most extensively studied, and its role in signalling transduction is widely accepted, but hundreds of other modifications have been identified to date, and new ones are still under identification. (mdpi.com)
On binding of insulinlike growth factors to the receptor, adaptor proteins, such as insulin-receptor substrate-1 (IRS-1) and IRS-2, are recruited to the phosphorylation site of the cytoplasmic domain ( 19 - 21 ). (snmjournals.org)
Palmitate impairs insulin signaling by a decrease in insulin‐stimulated phosphorylation of Akt that corresponds to an 87% decrease in insulin‐stimulated glucose uptake in HL‐1 cardiomyocytes. (mdm2-inhibitors.com)
Free circulating insulin activates insulin receptors on the surface of target cells eliciting a signaling cascade initiated by the activation of insulin receptor substrates (IRS 1-4) followed by phosphorylation of phosphoinositide 3-kinase (PI3K), which manages metabolic response including PDK1 and Akt stimulation by phosphorylation. (encyclopedia.pub)

Insulin receptor substrate 1 plays a key role in transmitting signals from the insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF-1) to intracellular pathways PI3K / Akt and Erk MAP kinase pathways. (wikipedia.org)
This enables IRS-1 to activate several signalling pathways, including the PI3K pathway and the MAP kinase pathway. (wikipedia.org)
On the other hand, an increase in Ca 2+ induces eNOS translocation from the cell membrane to the cytosol or Golgi complex ( 8 ), where it is phosphorylated and fully activated by protein kinases that reside in caveolae, such as p38 mitogen-activated protein kinase, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), cAMP-dependent protein kinase A, and 5′ AMP-activated protein kinase ( 7 ). (diabetesjournals.org)
Conversely, inhibition of PVA neuronal activity using DREADDs (designer receptors exclusively activated by designer drugs) or inactivation of PVA extracellular signal-regulated kinase at the critical time window blunted mechanical hyperalgesia in chronic pain models. (iasp-pain.org)
The key components of the Igf 1 receptor signaling pathway include the IGF-1 receptor, insulin receptor substrate proteins (IRS), phosphatidylinositol 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). (ebiwinner.com)
One key insight into the Igf 1 receptor signaling pathway is the involvement of phosphoinositide 3-kinase (PI3K) and Akt. (ebiwinner.com)
Dietary sugars trigger the production of insulin or insulin-like peptides which are sensed by Insulin receptors at the cell surface and initiate a kinase cascade, leading to the activation of the downstream kinase Akt (PKB), the translocation of GLUT4 glucose transporters to the cell surface, and ultimately glucose uptake. (biomedcentral.com)
Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (embl.de)
Subsequently, the phosphatidylinositol-3-kinase and mitogen-activated protein kinase pathways can be activated, resulting in proliferation and inhibition of apoptosis ( 13 , 14 ). (snmjournals.org)
Among them, the sirtuin, AMP-activated protein kinase, mammalian target of rapamycin, p53, and insulin/insulin-like growth factor-1 signaling pathways are most widely studied. (frontiersin.org)
Insulin receptor substrates (IRSs) are major targets of IGF-I receptor (IGF-IR) tyrosine kinase activated by IGFs, and are known to play important roles in the activation of downstream signaling pathways, such as the Erk1/2 pathway. (oncotarget.com)
What are physical characteristics found in all tyrosine kinase receptors? (flashcardmachine.com)
How is the insulin tyrosine kinase receptor unusual? (flashcardmachine.com)
How is a tyrosine kinase receptor activated? (flashcardmachine.com)
ROS decreased the mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase signaling, while overexpression of IRS-1 attenuated this inhibition. (biomedcentral.com)
ROS-mediated autophagy may occur via inhibition of IRS-1/phosphatidylinositol 3-kinase/mTOR signaling. (biomedcentral.com)
The main IRS-1 downstream signaling pathways include type I phosphatidylinositol 3-kinase (PI3K)/Akt (PKB: protein kinase B), mammalian target of rapamycin (mTOR), and mitogen activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK). (biomedcentral.com)
The class 1A phosphoinositide 3-kinase (PI3K) beta (PI3Kβ) is functionally unique in the ability to integrate signals derived from receptor tyrosine kinases (RTKs), heterotrimeric guanine nucleotide-binding protein (G-protein)-coupled receptors (GPCRs), and Rho-family GTPases. (elifesciences.org)
Previous experiments have not been able to elucidate whether interactions with membrane-tethered proteins primarily control PI3Kβ localization versus directly modulate lipid kinase activity. (elifesciences.org)
To address this gap in our understanding of PI3Kβ regulation, we established an assay to directly visualize and decipher how three binding interactions regulate PI3Kβ when presented to the kinase in a biologically relevant configuration on supported lipid bilayers. (elifesciences.org)
Outcomes Diet-induced weight problems reduced cardiac blood sugar fat PTK787 2HCl burning capacity GLUT and AMP-activated proteins kinase (AMPK) amounts which was connected with increased degrees of macrophages toll-like receptor 4 suppressor of cytokine signaling 3 (SOCS3) and cytokines in center. (cancer-ecosystem.com)
Receptor function will be assessed by assaying its tyrosine kinase activity. (diabetestalk.net)
An Introduction and Overview of RON Receptor Tyrosine Kinase Signaling. (uc.edu)
Insulin signaling affects multiple downstream pathways including mitogen-activated protein kinase (MAPK), which controls growth, sterol regulatory element-binding protein 1 (SREBP-1), which stimulates the synthesis of lipid and cholesterol as well as the family of Forkhead (FOXO) transcription factors regulating metabolism and autophagy [ 9 ] [ 10 ] . (encyclopedia.pub)
A fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome was conducted in a Drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. (sdbonline.org)

Altogether, these mechanisms stimulate IRS-1 degradation and insulin resistance. (wikipedia.org)
During insulin resistance induced by hyperglycemia, glucose accumulates in tissues as its hexosamine metabolite UDP-GlcNAc. (wikipedia.org)
Metabolic risk factors, such as obesity, insulin resistance, and type 2 diabetes (T2D), can initiate and accelerate endothelial dysfunction leading to cardiovascular disease (CVD) ( 1 ). (diabetesjournals.org)
Metabolic syndrome is consists of abdominal obesity, hyperglycemia, insulin resistance, hypertriglyceridemia, low HDL cholesterol and hypertension and is an important risk factor for atherosclerotic cardiovascular disease [ 16 ]. (biomedcentral.com)
Insulin resistance is a major metabolic feature of obesity and is a key factor in the etiology of a number of diseases, including type 2 diabetes. (jci.org)
In this review, we discuss potential mechanisms by which brief nutrient excess and obesity lead to insulin resistance and propose that these mechanisms of action are different but interrelated. (jci.org)
We then discuss how obesity leads to insulin resistance via a complex interplay among systemic fatty acid excess, microhypoxia in adipose tissue, ER stress, and inflammation. (jci.org)
In particular, we focus on the hypothesis that the macrophage is an important cell type in the propagation of inflammation and induction of insulin resistance in obesity. (jci.org)
Insulin resistance is defined as an inadequate response by insulin target tissues, such as skeletal muscle, liver, and adipose tissue, to the physiologic effects of circulating insulin. (jci.org)
The causes of insulin resistance can be genetic and/or acquired. (jci.org)
Nonetheless, it is likely that any genetic component must interact with environmental factors in order for insulin resistance to develop into a pathophysiologically meaningful abnormality. (jci.org)
In the presence of a robust compensatory insulin secretory response to insulin resistance, glucose levels can remain relatively normal. (jci.org)
Taken together, the inhibition of hsa_circ_0046060 expression in exosomes from GDM-derived UMSCs can alleviate GDM by reversing abnormal glucose metabolism and insulin resistance in vivo and in vitro . (hindawi.com)
Increased insulin resistance (IR) and immune tolerance in pregnant women result in metabolic and immunological alterations, which may aggravate the development of gestational diabetes mellitus (GDM). (hindawi.com)
Polycystic ovary syndrome (PCOS) is a heterogeneous familial disorder characterized by insulin resistance and an increased risk of type 2 diabetes mellitus (T2DM), a disorder with epidemic public health significance. (pitt.edu)
Generalized linear modeling was utilized to test for association of genotype with subclinical measures of CHD, including insulin resistance (HOMA-IR) and C-reactive protein (CRP). (pitt.edu)
In conclusion, the significant risk of T2DM attributed to women by PCOS was not explained by genetic SNPs analyzed here, however, a significant association of G972R and G972RxPCOS interaction with CRP concentrations was found, further supporting the growing body of evidence of associations between insulin resistance and systemic inflammation. (pitt.edu)
Thus, cytohesin inhibition results in hepatic insulin resistance. (nature.com)
Because insulin resistance is among the earliest pathological changes in type 2 diabetes, our results show the potential of chemical biology for dissecting the molecular pathogenesis of this disease. (nature.com)
Impaired cytohesin function results in hepatic insulin resistance. (nature.com)
Numerous epidemiological studies have shown that both type 2 diabetes (DM2) and insulin resistance are risk factors for AD. (nih.gov)
Many patients with AD exhibit reduced cerebral glucose metabolism similar to patients with DM2, making insulin resistance a contributing factor to the pathophysiology of AD. (nih.gov)
Increased lipid accumulation and mitochondrial dysfunction within skeletal muscle have been shown to be strongly associated with insulin resistance. (biomedcentral.com)
A high-fat diet resulted in insulin resistance as well as accumulation of cytosolic lipid intermediates and down-regulation of MFN2 and CPT1 in skeletal muscle in rats, while MFN2 overexpression improved insulin sensitivity and reduced lipid intermediates in muscle, possibly by upregulation of CPT1 expression. (biomedcentral.com)
MFN2 overexpression can rescue insulin resistance, possibly by upregulating CPT1 expression leading to reduction in the accumulation of lipid intermediates in skeletal muscle. (biomedcentral.com)
Type 2 diabetes is characterized by insulin resistance (which affects skeletal muscle, liver and other insulin-sensitive tissues) and by defective insulin secretion [ 1 ]. (biomedcentral.com)
The hypothesis that insulin resistance is related to lipid accumulation in muscle dates back to studies reported 15-20 years ago showing that triglycerides accumulate in muscle in rats fed a high-fat diet, which is coincident with insulin resistance. (biomedcentral.com)
Since then the relevance of muscle lipid accumulation to insulin resistance in humans has been demonstrated, and basic studies have indicated plausible mechanisms whereby lipid accumulation could generate insulin resistance [ 5 ]. (biomedcentral.com)
It is characterized by a cluster of risk factors of atherosclerosis including insulin resistance, hyperinsulinemia, impaired glucose tolerance or type 2 diabetes, hypertension, dyslipidemia, and coagulation abnormalities. (erudit.org)
Its pathophysiology is likely to involve insulin resistance at the level of both skeletal muscle and visceral adipose tissue and altered fluxes of metabolic substrates between these tissues that in turn impair liver metabolism. (erudit.org)
Insulin level of resistance and diabetes are comorbidities of obesity and affect 1 in 10 adults in the United States. (mdm2-inhibitors.com)
for CAV3 raises susceptibility to palmitate‐induced global insulin resistance and causes cardiomyopathy. (mdm2-inhibitors.com)
In keeping with our additional outcomes Shape?5C demonstrates PALM‐induced lack of CAV3 causes insulin resistance in isolated cardiomyocytes. (mdm2-inhibitors.com)
Insulin resistance ( IR ) is a pathological condition in which cells either fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia . (wikipedia.org)
In states of insulin resistance, the same amount of insulin does not have the same effect on glucose transport and blood sugar levels. (wikipedia.org)
There are many causes of insulin resistance and the underlying process is still not completely understood. (wikipedia.org)
Risk factors for insulin resistance include obesity , sedentary lifestyle , family history of diabetes, various health conditions, and certain medications. (wikipedia.org)
Insulin resistance is considered a component of the metabolic syndrome . (wikipedia.org)
There are multiple ways to measure insulin resistance such as fasting insulin levels or glucose tolerance tests, but these are not often used in clinical practice. (wikipedia.org)
Insulin resistance can be improved or reversed with lifestyle approaches, such as exercise and dietary changes. (wikipedia.org)
There are a number of risk factors for insulin resistance, including being overweight or obese or having a sedentary lifestyle . (wikipedia.org)
[1] Various genetic factors can increase risk, such as a family history of diabetes, and there are some specific medical conditions associated with insulin resistance, such as polycystic ovary syndrome . (wikipedia.org)
Dietary factors are likely to contribute to insulin resistance. (wikipedia.org)
Foods that have independently been linked to insulin resistance include those high in sugar with high glycemic indices , low in omega-3 and fiber, and which are hyperpalatable which increases risk of overeating. (wikipedia.org)
The percentage of polyunsaturated fatty acids (PUFAs) is inversely correlated with insulin resistance. (wikipedia.org)
[3] It is hypothesized that increasing cell membrane fluidity by increasing PUFA concentration might result in an enhanced number of insulin receptors, an increased affinity of insulin to its receptors, and reduced insulin resistance. (wikipedia.org)
Vitamin D deficiency has also been associated with insulin resistance. (wikipedia.org)
Sedentary lifestyle increases the likelihood of development of insulin resistance. (wikipedia.org)
Studies have consistently shown that there is a link between insulin resistance and circadian rhythm, with insulin sensitivity being higher in the morning and lower in the evening. (wikipedia.org)
A mismatch between the circadian rhythm and the meals schedule, such as in circadian rhythm disorders , may increase insulin resistance. (wikipedia.org)
Some medications are associated with insulin resistance including corticosteroids , protease inhibitors (type of HIV medication), [11] and atypical antipsychotics . (wikipedia.org)
Being exposed to light during sleep has been shown to cause insulin resistance and increase heart rate. (wikipedia.org)
Many hormones can induce insulin resistance including cortisol , [14] growth hormone , and human placental lactogen . (wikipedia.org)
Cortisol counteracts insulin and can lead to increased hepatic gluconeogenesis , reduced peripheral utilization of glucose, and increased insulin resistance. (wikipedia.org)
Acute physiological elevation of IL-6 suppressed blood sugar metabolism and triggered insulin level of resistance by raising SOCS3 and via SOCS3-mediated inhibition of insulin receptor substrate (IRS)-1 and perhaps AMPK in center. (cancer-ecosystem.com)
Increasing evidence signifies the function of chronic irritation and macrophage activation in insulin level of resistance (8 9 A cohort of latest studies (10-13) showed boosts in macrophage infiltration and cytokine appearance in adipose tissues and their association with insulin level of resistance in obese human beings and animal versions. (cancer-ecosystem.com)
Nevertheless the function PTK787 2HCl of IL-6 in insulin level of resistance remains debatable generally because of its differential results on blood sugar fat burning capacity in skeletal muscles adipose tissues and liver organ (19). (cancer-ecosystem.com)
Regardless of the prosperity of information over the function of irritation in peripheral insulin level of resistance the influence of irritation on cardiac fat burning capacity is not previously addressed. (cancer-ecosystem.com)
Genetic ablation of diabetes-associated gene Ccdc92 reduces obesity and insulin resistance in mice. (uc.edu)
Our aim was to evaluate the prevalence of insulin resistance in Egyptian patients with chronic HCV genotype 4 infection, to assess factors associated with insulin resistance and to test the impact of insulin resistance on outcomes of treatment with pegylated interferon/ribavirin. (who.int)
This study confirms that insulin resistance affects treatment outcome, and thus HOMA-IR testing before initiation of therapy may be a cost-effective tool. (who.int)
Increased GH concentrations during early postpartum (PP) act as an antagonistic to insulin by enhancing lipolysis and developing insulin resistance (IR) to help direct nutrients from insulin-sensitive tissues to the lactating mammary gland [ 5 , 9 ]. (biomedcentral.com)
4 infection, to assess factors associated with insulin resistance and to test the impact of insulin resistance on outcomes of treatment with pegylated interferon/ribavirin. (who.int)
conditions such as insulin resistance in the most prevalent genotype in Egypt patients with HCV infection. (who.int)
Adding to this grow- genotype 4, to assess factors associated proportion of Egyptians estimated to be ing body of evidence, it is now suggested with insulin resistance in those patients chronically infected was 9.8% ( 1 ). (who.int)

Despite significant homology between IRS-1 and IRS-2, recent studies have revealed distinct functions for these adaptor proteins in regulating breast cancer progression. (spandidos-publications.com)
The insulin receptor substrate (IRS) proteins are a family of cytoplasmic adaptor proteins recognized for their role in insulin signaling. (biomedcentral.com)
Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. (sdbonline.org)

The selective inhibition of NF-κB-65 abolished the occupancy of IRS-2 to the cyclin D1 promoters. (spandidos-publications.com)
The hallmarks of impaired insulin sensitivity in these three tissues are decreased insulin-stimulated glucose uptake into skeletal muscle, impaired insulin-mediated inhibition of hepatic glucose production in liver, and a reduced ability of insulin to inhibit lipolysis in adipose tissue. (jci.org)
Molecular analysis of non-small cell lung cancer identifies subsets with different sensitivity to insulin-like growth factor I receptor inhibition. (omicsdi.org)
They regulate signalling though inhibition of phosphatases and induction of the activity of Stress Activated Protein Kinases, which themselves modulate feedbacks to insulin signalling and FOXO. (biomedcentral.com)
These include regulation of cell cycle, activation of mitochondrial pathway, induction of mitochondrial outer membrane permeabilization, induction of apoptosis, modulation of oxidative stress, amelioration of inflammation, modulation of insulin signaling and inhibition of angiogenesis. (mdpi.com)
Overexpression of IRS-1 resulted in inhibition of basal autophagy, and reduced oxidative stress-induced autophagy and cell death. (biomedcentral.com)
CONCLUSIONS Our results that nutrient tension activates cardiac irritation which IL-6 suppresses myocardial blood sugar fat burning capacity via inhibition of AMPK and IRS-1 underscore the key function of irritation in the pathogenesis of diabetic center. (cancer-ecosystem.com)
Isolated hepatocytes will be assayed for the insulin-sensitive activities of: amino acid transport, inhibition of protein degradation, and glucose incorporation in glycogen. (diabetestalk.net)

We demonstrated that depletion of endogenous IRS-2 by antisense strategies impaired cell proliferation after serum withdrawal, blunted PI3K/Akt and NF-κB activation in IGF-1 induced response in MCF-7 and BT-20 breast cancer cells. (spandidos-publications.com)
Nuclear IRS-2 interaction with NF-κB-p65 and PI3K binding tyrosine residues of IRS-2 are crucial for the NF-κB activities. (spandidos-publications.com)
Our studies suggest that IRS-2 plays a significant role by activating, at least in part, NF-κB via PI3K/Akt pathway in IGF-1-induced responses in breast cancer cells and the crosstalk between nuclear IRS-2 and NF-κB might be responsible for transcriptional progression of the breast cancer cells. (spandidos-publications.com)
Potential therapeutic targets in the Igf 1 receptor signaling pathway include the IGF-1 receptor itself, as well as downstream signaling molecules such as PI3K, AKT, and mTOR. (ebiwinner.com)
Upon activation of the receptor, PI3K is recruited to the receptor complex and phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). (ebiwinner.com)
The activation of both MAPK and PI3K signaling pathways has been implicated in the stimulation of proliferation by IRS-1 [ 11 ]. (biomedcentral.com)
The mechanism by which PI3Kβ prioritizes interactions with various membrane tethered signaling inputs, however, remains unclear. (elifesciences.org)
2016) . A cross-species study of PI3K protein-protein interactions reveals the direct interaction of P85 and SHP2 . (sdbonline.org)
These data revealed an unexpected direct binding of Corkscrew, the Drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e , the human ortholog of the p110 catalytic subunit. (sdbonline.org)

This study aimed to determine whether I3C or DIM could increase glucose uptake via enhanced insulin sensitivity in 3T3‐L1 adipocytes, as well as the mechanism involved. (researchgate.net)
Conclusions Our findings suggest that DIM may improve insulin sensitivity through the activation of the insulin signaling pathway, leading to enhanced glucose uptake. (researchgate.net)
DIM, a major metabolite of indole-3-carbinol, which is naturally produced in broccoli and cabbage, enhances glucose uptake through the improvement of insulin sensitivity in 3T3-L1 cells [13] . (researchgate.net)
Overall, we provide our integrative perspective regarding how nutrients and obesity interact to regulate insulin sensitivity. (jci.org)
Impaired glucose metabolism and insulin sensitivity have been linked to the pathogenesis of gestational diabetes mellitus (GDM). (hindawi.com)
This study aimed to identify molecular determinants of sensitivity of non-small cell lung cancer (NSCLC) to anti-insulin-like growth factor receptor (IGF-IR) therapy.A total of 216 tumor samples were investigated, of which 165 consisted of retrospective analyses of banked tissue and an additional 51 were from patients enrolled in a phase II study of figitumumab, a monoclonal antibody against IGF-IR, in stage IIIb/IV NSCLC. (omicsdi.org)
Applying this validated in?vitro cellular model we addressed the part of CAV3 in insulin level of sensitivity then. (mdm2-inhibitors.com)
Shape?5B clearly demonstrates that insulin‐stimulated blood sugar uptake Ki16425 Ki16425 was absent Ki16425 in siRNA‐transfected HL‐1 cells in comparison to scrambled siRNA control cells as a result further supporting a significant part of CAV3 in insulin level of sensitivity. (mdm2-inhibitors.com)
Shape 5 Lack of CAV3 abolishes insulin level of sensitivity in HL‐1 cells and in major isolated cardiomyocytes. (mdm2-inhibitors.com)
During early lactation, suppressed insulin sensitivity along with uncoupled GH/IGF-1 axis stimulates the mobilization of body fat reserves [ 4 , 5 ]. (biomedcentral.com)
It is well established that PP cows often exhibit symptoms similar to type 2 diabetes (T2DM), including elevated plasma free fatty acid concentrations and decreased sensitivity of tissue to the presence of insulin which plays a major role in the development of many metabolic disorders [ 10 ]. (biomedcentral.com)

IRS-1 signal transduction may be inhibited by SHP2 in some tissues. (wikipedia.org)
IRS-1 is phosphorylated on serine, threonine and tyrosine residues in a variety of tissues. (thermofisher.com)
Subsequently, normal cell-cell interactions between the tumor and surrounding tissues and immune cells begin to breakdown, leading to invasion and eventual metastasis to distant sites. (umassmed.edu)
However, the effects of chronic administration on insulin sensitive tissues in vivo is much less well studied. (diabetestalk.net)
Rats will be given vanadium, as sodium orthvanadate or vanadyl sulfate, in a liquid diet and a number of insulin-sensitive activities of target tissues measured and compared to control animals. (diabetestalk.net)
Type 2 diabetes (T2D) is characterized by hyperglycaemia and defects in insulin secretion and action at target tissues. (diabetestalk.net)
We sought to establish differences in global miRNA expression in two insulin-target tissues from inbred rats of spontaneously diabetic and normoglycaemic strains. (diabetestalk.net)
We used a miRNA microarray platform to measure global miRNA expression in two insulin-target tissues: liver and adipose tissue from inbred rats of spontaneously diabetic (Goto-Kakizaki [GK]) and normoglycaemic (Brown-Norway [BN]) strains which are extensively used in genetic studies of T2D. (diabetestalk.net)
Insulin is a key regulator of glucose uptake and utilization in insulin-responsive tissues. (encyclopedia.pub)
Insulin rapidly increases the expression of Per2 in insulin-sensitive tissues like the liver, muscle, or adipose tissue, but not the lung or brain [ 17 ] . (encyclopedia.pub)

Previous studies have found that DIM can improve type 2 diabetes by enhancing glucose uptake through the activation of insulin signaling in 3T3-L1 cells, and by lowering the plasma glucose levels in high-fat-diet-fed obese mice [13, 14]. (researchgate.net)
3,3′-diindolylmethane (DIM)-a natural compound produced from indole-3-carbinol, found in cruciferous vegetables-enhances glucose uptake by increasing the activation of the insulin signaling pathway in 3T3-L1 adipocytes. (researchgate.net)
Fat accumulation in muscle negatively impacts insulin-mediated glucose uptake. (biomedcentral.com)

The physiological functions of the Igf 1 receptor signaling pathway include regulation of growth and development, metabolism, tissue repair, and immune function. (ebiwinner.com)
SecinH3-treated mice show increased expression of gluconeogenic genes, reduced expression of glycolytic, fatty acid and ketone body metabolism genes in the liver, reduced liver glycogen stores, and a compensatory increase in plasma insulin. (nature.com)
Insulin-like growth factor-1 (IGF-1), a member of a family of growth factors that are structurally closely related to pro-insulin, has shown profound effects on chondrocyte biological behavior and fundamentally regulates cartilage matrix metabolism during cartilage repair. (biomedcentral.com)
IL-6 reduces blood sugar fat burning capacity by suppressing AMPK and insulin PTK787 2HCl receptor substrate (IRS)-linked insulin signaling in center whereas IL-6-deficient mice are covered from diet-induced modifications in blood sugar metabolism. (cancer-ecosystem.com)
The actual fact that severe lipid infusion escalates the inflammatory response and impairs myocardial blood sugar metabolism like the ramifications of high-fat nourishing suggests the function of nutritional tension in the activation of toll-like receptor (TLR) 4 signaling and irritation in center. (cancer-ecosystem.com)
and 4) to determine if vanadium affects insulin metabolism. (diabetestalk.net)
Akt pathways have effects on apoptosis, protein synthesis, metabolism and cell cycle. (springer.com)
This study identified that the protein most commonly affected in Noonan syndrome, the phosphatase SHP2, known in Drosophila as corkscrew (CSW) , controls life span, triglyceride levels, and metabolism without affecting ERK signaling pathway. (sdbonline.org)

It is a 131 kDa protein with amino acid sequence of 1242 residues. (wikipedia.org)
Multiple tyrosine residues of IRS-1 itself are then phosphorylated by these receptors. (wikipedia.org)
Moreover, tyrosine residues of YXXM motifs, which recruit downstream effectors, also contributed to IRS-1 self-association and LLPS. (nature.com)
IRS-1 contains no transmembrane domain but an amino-terminal pleckstrin homology (PH) and a phosphotyrosine-binding domain (PTB), followed by a carboxyl-terminal region which is enriched in Ser and Thr residues 28 . (nature.com)
We further identified that the 301-600 residues, as a self-association region (SAR), is essential to the formation of IRS-1 droplets and the transduction of insulin/IGF signaling. (nature.com)
CAV -1 is an integral membrane protein found in caveolae, omega-shaped invaginations of the plasma membrane that form a subdomain of cholesterol- and sphingolipid-rich lipid rafts.Cav1 gene is localized to locus D7S522 of human chromosome 7q31.1In vivo, two isoforms of Cav1 are known to exist: α-caveolin that contains residues 1-178 and β-caveolin that contains residues 32-178. (diff.org)
Brefeldin A acts to stabilize an abortive ARF-GDP-Sec7 domain protein complex: involvement of specific residues of the Sec7 domain. (nature.com)

In contrast to the activated epidermal growth factor receptor that binds the GRB2-Sos complex directly, activation of the insulin receptor results in the interaction of GRB2-Sos with IRS-1 and Shc, thus linking the insulin receptor to Ras signaling pathways. (nih.gov)

Insulin receptor substrate 1 (IRS-1) is a signaling adapter protein that in humans is encoded by the IRS1 gene. (wikipedia.org)
As a critical node for insulin/IGF signaling, insulin receptor substrate 1 (IRS-1) is essential for metabolic regulation. (nature.com)
Impairment of IRS-1 LLPS attenuated its positive effects on insulin/IGF-1 signaling. (nature.com)
Our findings delineate a mechanism in which LLPS of IRS-1-mediated signalosomes serves as an organizing center for insulin/IGF-1 signaling and implicate the role of aberrant IRS-1 LLPS in metabolic diseases. (nature.com)
In addition to maintaining specific organelle structures, phase separation enables hub proteins to assemble signalosomes which promote the speed of signaling outputs 11 , 12 . (nature.com)
Insulin receptor substrate (IRS) proteins play essential roles in mediating insulin/IGF signaling by recruiting a series of downstream effectors 23 . (nature.com)
Since these intrinsically disordered regions, which are conformationally dynamic and do not adopt stable secondary or tertiary structures, are often essential for mediating the phase transition of proteins 9 , it is therefore of interest to consider if the C-terminus of IRS-1 is involved in phase separation and to further delineate such implications upon insulin/IGF signaling. (nature.com)
The IGF-1 receptor signaling pathway plays a crucial role in cell growth, proliferation, and survival. (ebiwinner.com)
Learn more about the IGF-1 receptor signaling pathway and its potential as a therapeutic target. (ebiwinner.com)
The Igf 1 receptor signaling pathway is a cellular signaling pathway that is activated by the binding of insulin-like growth factor 1 (IGF-1) to its receptor on the cell surface. (ebiwinner.com)
What are the key components of the Igf 1 receptor signaling pathway? (ebiwinner.com)
How does the Igf 1 receptor signaling pathway regulate cell growth and survival? (ebiwinner.com)
The Igf 1 receptor signaling pathway regulates cell growth and survival by activating downstream signaling molecules that promote cell proliferation, inhibit apoptosis, and stimulate protein synthesis. (ebiwinner.com)
Dysregulation of the Igf 1 receptor signaling pathway has been implicated in various diseases, including cancer, diabetes, and neurodegenerative disorders. (ebiwinner.com)
What are the potential therapeutic targets in the Igf 1 receptor signaling pathway? (ebiwinner.com)
The Igf 1 receptor signaling pathway is regulated by various mechanisms, including ligand availability, receptor expression and activation, as well as negative feedback loops and cross-talk with other signaling pathways. (ebiwinner.com)
What are the current research efforts focused on in the field of Igf 1 receptor signaling pathway? (ebiwinner.com)
Current research efforts in the field of Igf 1 receptor signaling pathway are focused on understanding the molecular mechanisms underlying its regulation, identifying novel therapeutic targets, and developing strategies to modulate its activity for the treatment of various diseases. (ebiwinner.com)
This pathway is activated by the binding of insulin-like growth factor 1 (IGF-1) to its receptor, leading to the activation of downstream signaling cascades. (ebiwinner.com)
Understanding the Igf 1 receptor signaling pathway has important implications for various diseases, including cancer. (ebiwinner.com)
In conclusion, the Igf 1 receptor signaling pathway is a complex and highly regulated pathway that plays a critical role in various biological processes. (ebiwinner.com)
The insulin-like growth factor (IGF) signaling pathway has been implicated in the pathogenesis of numerous tumor types, including non-small cell lung cancer (NSCLC). (omicsdi.org)
Insulin/IGF-I signaling pathways enhances tumor cell invasion through bisecting GlcNAc N-glycans modulation. (omicsdi.org)
The researchers measured the blood levels of a phosphorylated form of a signaling protein called type 1 insulin receptor substrate (IRS-1) in neurally derived plasma exosomes. (nih.gov)
The insulin-like growth factor (IGF) signaling pathway has been implicated in articular cartilage repair. (biomedcentral.com)
Thus these findings suggest that loss of CAV3 interferes with downstream insulin signaling and lipid uptake implicating CAV3 like a regulator of the IR and regulator of lipid uptake in the heart. (mdm2-inhibitors.com)
These results suggest that CAV3 and IR are in close proximity in HL‐1 cell membrane and most likely bind directly to each other (Fig.?4B) and this interaction may play important roles in the process of IR activation and subsequent signaling. (mdm2-inhibitors.com)
ROS inactivates IRS-1 mediated signaling and reduces intracellular IRS-1 concentrations. (biomedcentral.com)
To decipher how amplification of PI(3,4,5)P 3 arises from the relay of signals between cell surface receptors, lipids, and peripheral membrane proteins, we must understand how membrane localization and activity of PI3Ks is regulated by different signaling inputs. (elifesciences.org)
The main molecular pathways affected by CR include mTOR, insulin signaling, AMPK, and sirtuins. (encyclopedia.pub)
Furthermore, a genome-wide RNAi screen for genes that regulate cellular clock functions in human cells identified the insulin signaling pathway as the most overrepresented pathway [ 15 ] . (encyclopedia.pub)
A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway. (sdbonline.org)
Noonan syndrome and related disorders are caused by mutations in genes encoding for proteins of the RAS-ERK1/2 signaling pathway, which affect development by enhanced ERK1/2 activity. (sdbonline.org)
This study found that CSW loss-of-function mutations extended life span by interacting with components of the insulin signaling pathway and impairing AKT activity in adult flies. (sdbonline.org)

Critical for cellular organization, phosphatidylinositol phosphate (PIP) lipids regulate the localization and activity of numerous proteins across intracellular membranes in eukaryotic cells ( Di Paolo and De Camilli 2006 ). (elifesciences.org)

We have developed a model of insulin signalling in rodent adipocytes that includes both transcriptional feedback through the Forkhead box type O (FOXO) transcription factor, and interaction with oxidative stress, in addition to the core pathway. (biomedcentral.com)
Insulin and oxidative stress combined produce a lower degree of activation of insulin signalling than insulin alone. (biomedcentral.com)
Fasting (nutrient withdrawal) and weak oxidative stress upregulate antioxidant defences while stronger oxidative stress leads to a short term activation of insulin signalling but if prolonged can have other effects including degradation of the insulin receptor substrate (IRS1) and FOXO. (biomedcentral.com)
At high insulin the protective effect of moderate oxidative stress may disappear. (biomedcentral.com)
Oxidative stress can have effects that are both up- and down-regulatory on insulin signalling. (biomedcentral.com)
Our results suggest that overexpression of IRS-1 promotes cells growth, inhibits basal autophagy, reduces oxidative stress-induced autophagy, and diminishes oxidative stress-mediated autophagy-dependent cell death. (biomedcentral.com)
In this study, a computational model of AD and PD have been modelled using biochemical systems theory, and shows how Tumour Necrosis Factor alpha (TNF훼) regulated neuroinflammation, oxidative stress and insulin pathways can dysregulate its downstream signalling cascade that lead to neurodegeneration observed in AD and PD. (springeropen.com)
Simulations suggest insulin may be an important factor identifying neurodegeneration in AD and PD, through its action along with the neuroinflammation and oxidative stress. (springeropen.com)
Given the role towards better design of real experiments, accumulation of oligomers of mutated proteins in AD and PD activating microglia and secreting TNFα along with other cytokines map to oxidative stress that led to cell death. (springeropen.com)

There is evidence that insulin-resistant obese individuals with type 2 diabetes have approximately 30% fewer mitochondria in their skeletal muscle than age-matched healthy controls [ 12 ]. (biomedcentral.com)

Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. (embl.de)

IRS-1 plays important biological function for both metabolic and mitogenic (growth promoting) pathways: mice deficient of IRS1 have only a mild diabetic phenotype, but a pronounced growth impairment, i.e. (wikipedia.org)
The metabolic disease-associated G972R mutation impaired the self-association and LLPS of IRS-1. (nature.com)
Importantly, metabolic disease-derived G972R mutation results in a reduced ability of LLPS, potentially implicating the involvement of aberrant IRS-1 phase separation in various metabolic disorders. (nature.com)
There may be multiple metabolic causes for increased cytosolic lipid accumulation in muscle in insulin-resistant states. (biomedcentral.com)

IRS-1, a major substrate of the insulin receptor, is phosphorylated in response to stimulation of cells by insulin, insulin-like growth factor 1 (IGF-1) and interleukin 4 (IL-4). (thermofisher.com)

Insulin-induced activation of extracellular signal-regulated kinases [ERKs, also known as mitogen-activated protein (MAP) kinases] is mediated by Ras. (nih.gov)

IRS-1 integrates signalling from insulin receptor (InsR), insulin-like growth factor-1 receptor (IGF1R) and many other cytokine receptors and is elevated in β-catenin induced cells. (wikipedia.org)
Further analysis showed that they largely control the activities of genes that encode cytokine and cytokine receptors, which enable T cells to communicate with other cells and mount an immune response. (nih.gov)

In response to insulin stimulation, this complex bound to tyrosine-phosphorylated IRS-1 (insulin receptor substrate-1) and Shc. (nih.gov)
IRS-1 was the first of these to be identified as a 185 kDa protein that is detectable by immunoblot analysis in response to insulin stimulation [ 1 ]. (biomedcentral.com)

AMPK pathways inhibit biosynthetic pathways with energy consumption, such as protein, fatty acid and glycogen synthesis. (springer.com)

Cav1 has also been localized to the nucleus of ovarian carcinoma cells where it binds directly to promoter regions of the cyclin D1 and folate receptor genes. (diff.org)
Mouse protein citron, a putative rho/rac effector that binds to the GTP-bound forms of rho and rac. (embl.de)
IRS-1 protein binds to several oncogene proteins. (biomedcentral.com)

GM-CSF is also involved in bone cancer pain development by regulating tumor-nerve interactions, remodeling of peripheral nerves and sensitization of damage-sensing (nociceptive) nerves. (iasp-pain.org)
Further, the postprandial release of insulin resets peripheral clocks by regulating the expression of core circadian genes. (encyclopedia.pub)

IGF-1 stimulation enhanced IRS-1 phase separation which then recruited downstream effectors to form insulin/IGF signalosomes. (nature.com)

How is a receptor-ligand binding curve determined? (flashcardmachine.com)
Describe the three lines on a receptor-ligand binding curve? (flashcardmachine.com)

Type 1 diabetes mellitus (insulin-dependent diabetes) is characterized by hyperglycemia caused by an insulin deficiency. (researchgate.net)

Results DIM, but not I3C, increased adipocyte differentiation through upregulation of peroxisome proliferator‐activated receptor γ and CCAAT/enhancer‐binding protein α. (researchgate.net)
Genetic variants analyzed for association with PCOS and subclinical coronary heart disease (CHD) risk measures were the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) single nucleotide polymorphism (SNP) P12A, insulin receptor substrate-1 (IRS-1) SNP G972R, one novel SNP of lipoprotein lipase (LPL), and three novel SNPs from acetyl-CoA carboxylase-beta (ACC-beta). (pitt.edu)
Members of the family of nuclear receptors, the three peroxisome proliferator-activated receptors (PPARs), PPARα, PPARβ/δ, and PPARγ take part in the modulation of these pathways. (encyclopedia.pub)

The cellular protein levels of IRS-1 are regulated by the Cullin-7 E3 ubiquitin ligase, which targets IRS-1 for ubiquitin mediated degradation by the proteasome. (wikipedia.org)

Insulin activates Ras primarily by increasing the rate of guanine nucleotide-releasing activity. (nih.gov)
Donaldson, J. G., Finazzi, D. & Klausner, R. D. Brefeldin A inhibits Golgi membrane-catalysed exchange of guanine nucleotide onto ARF protein. (nature.com)
Morinaga, N., Tsai, S.-C., Moss, J. & Vaughan, M. Isolation of a brefeldin A-inhibited guanine nucleotide-exchange protein for ADP ribosylation factor (ARF) 1 and ARF3 that contains a Sec7-like domain. (nature.com)
Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and Saccharomyces cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr. (embl.de)

Le tissu adipeux sécrète, en effet, une grande variété de molécules biologiquement actives agissant pour prévenir l'accumulation délétère de lipides et la modulation de l'insulinorésistance. (erudit.org)
Altogether, our results indicated an improved glucose and insulin status along with the modulation of the somatotropic axis and glucose and insulin response to IVGTT in dairy goats supplemented with 2 and 4 g/d BBR. (biomedcentral.com)

Microtubule-associated protein MAP1LC3C regulates lysosomal exocytosis and induces zinc reprogramming in renal cancer cells. (uc.edu)
It is concluded that CSW normally regulates life span and that mutations in SHP2 are expected to have critical effects throughout life by insulin-dependent mechanisms in addition to the well-known RAS-ERK1/2-dependent developmental alterations. (sdbonline.org)

Ser/Thr protein kinases such as the Akt/Rac family, the beta-adrenergic receptor kinases, the mu isoform of PKC and the trypanosomal NrkA family. (embl.de)
Tyrosine protein kinases belonging to the Btk/Itk/Tec subfamily. (embl.de)

Here, we show that insulin-induced activation of ERKs was enhanced by stable overexpression of growth factor receptor-bound protein 2 (GRB2) but not by overexpression of GRB2 proteins with point mutations in the Src homology 2 and 3 domains. (nih.gov)
Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
What is the function of a protein with SRC homology-2 domains? (flashcardmachine.com)

Some evidence shows that TCF/LEF-β-catenin complexes directly regulate IRS-1. (wikipedia.org)
We discuss how pathways that "sense" nutrients within skeletal muscle are readily able to regulate insulin action. (jci.org)

Polymerase chain reaction-Restriction Fragment Length Polymorphism was performed to analyze IRS-1 gene Gly972Arg genotype. (biomedcentral.com)

Caveolin-1 (Cav1) is a 22 KDa multifunctional scaffolding protein with multiple binding partners that is associated with cell surface caveolae and the regulation of lipid raft domains. (diff.org)
Acute lipid infusion triggered inflammation and elevated local degrees of macrophages C-C theme chemokine receptor 2 SOCS3 and cytokines in center. (cancer-ecosystem.com)
There are two types of hormones secreted in the endocrine system: Steroidal (or lipid based) and non-steroidal, (or protein based) hormones. (diabetestalk.net)

A) HL‐1 cells had been transfected with 100?pmol of siRNA using lipofectamine 2000 and collected for european blotting 20?h … Insulin‐3rd party activation of IR substrate‐1 (IRS‐1) and reduced Akt activation by palmitate Previously we've reported that palmitate diet plan nourishing induces a lack of cardiac. (mdm2-inhibitors.com)

The IGF-1R is a transmembrane receptor expressed in many human cancers, including 36% of all triple-negative breast carcinomas ( 11 ). (snmjournals.org)
What is the most common activity found intrinsic to transmembrane receptors? (flashcardmachine.com)

Moreover, a dominant negative form of Ras (with Ser17 substituted with Asn) blocked insulin-induced activation of ERKs in cells that overexpressed GRB2. (nih.gov)

Skeletal muscle is quantitatively the major contributor to whole body insulin-mediated glucose disposal. (biomedcentral.com)

IRS-1 dominant-negative mutant functions as tumor suppressor, whereas ectopic IRS-1 stimulates oncogenic transformation. (wikipedia.org)
Our data afford a plausible explanation for IRS-1 involvement in tumor initiation and progression. (biomedcentral.com)

In addition, IGF-1 promote nuclear translocation of IRS-2 and NF-κB in MCF-7 and BT-20 cells. (spandidos-publications.com)

IGF-1 is a member of a family of growth factors that are structurally closely related to pro-insulin and can promote chondrocyte proliferation, enhance matrix production, and inhibit chondrocyte apoptosis. (biomedcentral.com)
Insulin-like growth factors (IGFs) have been shown to induce proliferation of many types of cells. (oncotarget.com)

Other inhibitory pathways include SOCS proteins and O-GlcNAcylation of IRS-1. (wikipedia.org)

NO production in response to various factors, such as increased shear stress, is mediated by endothelial nitric oxide synthase (eNOS), which is constitutively expressed in endothelial cells (ECs) and is tightly controlled by various membrane-bound receptors and regulatory proteins under physiological conditions ( 3 ). (diabetesjournals.org)
To achieve this ordering, many cell cycle-regulatory proteins are expressed exclusively when their functions are needed. (umassmed.edu)
The Benanti lab is interested in understanding why cyclical expression of key regulatory proteins is important for maintaining a stable genome. (umassmed.edu)

Human recombinant protein fragment corresponding to amino acids 1-280 of human IRS1 produced in E.coli. (thermofisher.com)

They also control the allocation of energy and biological substrates to somatic growth, maintenance and repair, and so implicitly underlie theories of ageing such as the Disposable Soma Theory [ 1 ] which are based on the idea of trade-offs between these processes. (biomedcentral.com)

In a cross-sectional study of 48 AD patients without diabetes, 20 cognitively normal diabetic patients, 16 patients with frontotemporal dementia, and 84 cognitively normal controls, researchers found that dysfunctionally phosphorylated insulin receptor substrate-1 (IRS-1), a neuronal protein, is detectable in blood using exosome-based technology and may be able to predict AD up to 10 years before the appearance of symptoms. (medscape.com)

Interestingly, although the C-terminus of IRS-1 is essential for modulating the activation and stability of IRS-1, it is largely unstructured 29 . (nature.com)
Cherfils, J. & Chardin, P. GEFs: structural basis for their activation of small GTP-binding proteins. (nature.com)
Knockdown of USP9X suppressed basal activation of the Erk1/2 pathway, which was significantly restored by exogenous expression of IRS-2 but not by IGF-IR, suggesting that the stabilization of IRS-2 by USP9X is critical for basal Erk1/2 activation. (oncotarget.com)
Taken all together, our findings indicate that USP9X is required for the promotion of prostate cancer growth by maintaining the activation of the Erk1/2 pathway through IRS-2 stabilization. (oncotarget.com)

The application of SecinH3 in human liver cells showed that insulin-receptor-complex-associated cytohesins are required for insulin signalling. (nature.com)
Out of 29 liver tissue sections examined, 14 had a low level of expression of insulin receptor type 1 by immunohistochemical studies. (who.int)
The uncoupling of the somatotropic axis is marked by lower expression of growth hormone receptor (GHR) in the liver and consequently decreased IGF-1 synthesis in the liver [ 6 ]. (biomedcentral.com)

Hepatocytes and adipocytes will be isolated from animals and insulin binding analyzed by Scatchard plots. (diabetestalk.net)

IRS-1 knockout mice only reach 50% of the weight of normal mice. (wikipedia.org)
In this study, we investigated whether DIM could improve insulin-dependent diabetes and nephropathy in streptozotocin (STZ)-induced diabetic mice. (researchgate.net)
To aid these in?vitro data with in?vivo experiments we utilized CAV1 null mice fed regular or high‐extra fat diet programs and isolated cardiomyocytes after 12?weeks to check their insulin‐dependent blood sugar uptake rates. (mdm2-inhibitors.com)
Accordingly, the impact of CR on plasma IGF-1 and insulin level is compromised in mice deficient for Bmal1 [ 16 ] . (encyclopedia.pub)

Anatomy9

Organisms2

Diseases3

Chemicals and Drugs34

Analytical, Diagnostic and Therapeutic Techniques and Equipment2

Phenomena and Processes10

Information Science2

Phosphorylation26

Kinase25

Resistance65

Adaptor proteins3

Inhibition8

PI3K9

Sensitivity11

Tissues10

Glucose uptake3

Metabolism8

Residues7

Epidermal Growth F1

Signaling34

Intracellular1

Oxidative stress9

Type 2 diabet1

Signal transduction1

Metabolic4

Major substrate1

Extracellular1

Cytokine receptors2

Response to insulin stimulation2

AMPK1

Binds3

Peripheral2

Stimulation1

Ligand2

Hyperglycemia1

Peroxisome3

Degradation1

Guanine4

Modulation2

Regulates2

Kinases2

Homology3

Regulate2

Genotype1

Lipid3

Induces1

Transmembrane2

Cells that overexpressed1

Skeletal muscle1

Tumor2

Nuclear translocation1

Proliferation2

Pathways include1

Regulatory proteins3

IRS11

Biological1

Neuronal1

Activation4

Liver3

Adipocytes1

Mice4