A database built with INDRA combining content from numerous readers and databases. This page allows you to curate the loaded statements. For more information please see the manual.

IndraLab

Statements

databases
phosphosite cbn pc11 biopax bel_lc signor biogrid tas lincs_drug hprd trrust | geneways tees isi trips rlimsp medscan sparser reach
reading

INS affects IRS1
1 1 | 12 25
INS decreases the amount of IRS1. 10 / 38
1 | 12 25
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"While Irs2 expression is suppressed by insulin at the transcriptional level, Irs1 expression remains intact and is not downregulated by insulin XREF_BIBR XREF_BIBR XREF_BIBR."
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"On the other hand, PKCzeta or PKCiota and lambda overexpression attenuates the insulin induced phosphorylation of AKT, and decreases the protein level of IRS1, which suggests a diminished signaling cascade initiated from IRS1 upon insulin treatment (Figs."
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"When cells were exposed to both insulin and dexamethasone, the effect of insulin to reduce insulin receptor and IRS-1 levels and insulin stimulated IRS-1 phosphorylation dominated."
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"Prolonged insulin stimulation reduced IRS-1 levels in WT but not in SIN1 -/- (XREF_FIG)."
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"The results showed that 100nM insulin could induce SOCS3 mRNA expression but not protein expression, and overexpression of SOCS3 decreased IRS1 protein level, insulin stimulated IRS1 tyrosine phosphorylation, PI3K activation, and Akt phosphorylation, but increased IRS1 serine phosphorylation in porcine primary adipocytes."
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"Insulin resistance was induced by palmitic acid (PA) in human HK-2 cells, shown as the decrease of insulin stimulated AKT phosphorylation, glucose transporter-4 (GLUT4), glucose uptake and enhanced phosphorylation of insulin receptor substrate 1 (IRS-1) at site serine 307 (pIRS-1ser307) and downregulated expression of IRS-1."
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"Insulin decreased mRNA expression of IRS-1 by 72% (from 0.75 +/- 0.06 to 0.21 +/- 0.04 relative units; P < 0.001), IRS-2 by 71% (from 0.55 +/- 0.10 to 0.16 +/- 0.08 relative units; P < 0.03), and Shc by 25% (from 0.95 +/- 0.04 to 0.71 +/- 0.04 relative units; P < 0.01) vs. baseline as demonstrated in the control subjects."
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"Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression."
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"Finally, GPE prevented TNFalpha induced expression of protein tyrosine phosphatase (PTP)-1B and phosphorylation of serine residue 307 of insulin receptor substrate-1 (IRS-1), which are negative regulators of insulin sensitivity, and suppression of insulin stimulated glucose uptake."
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"IL1beta down-regulates insulin receptor substrate 1 expression, inhibiting insulin induced AKT phosphorylation and glucose uptake in adipocytes [XREF_BIBR]."
Transcriptionally active INS decreases the amount of IRS1. 1 / 1
1 |
biopax:ctd
No evidence text available
IRS1 is modified
| 28 5
IRS1 is degraded. 10 / 33
| 28 5
trips
"Insulin-induced degradation of IRS-1 has been well documented, both in cells as well as in patients with diabetes."
trips
"Our data suggest that the differential degradation of IRS-1 and IRS-2 contributes to their distinct modes of action and the increased neuroprotective effects of IRS-2 in this report are due, in part, to its resistance to caspase-mediated degradation."
trips
"Phosphorylation of IRS-1 on Ser307, which leads to subsequent IRS-1 degradation, was stimulated by angiotensin II."
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"We show that UDCA inhibits proliferation of nontransformed intestinal epithelial cells by inducing a sustained hyperphosphorylation of ERK1 kinase which slows down the cell cycle and reduces expression of Irs-1 protein."
trips
"Negative feedback regulation of insulin signaling involves ubiquitin-dependent degradation of insulin receptor substrate 1 (IRS1)."
trips
"Here we show in mice that muscle-specific mitsugumin 53 (MG53; also called TRIM72) mediates the degradation of the insulin receptor and insulin receptor substrate 1 (IRS1), and when upregulated, causes metabolic syndrome featuring insulin resistance, obesity, hypertension and dyslipidaemia."
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"On the other hand, PKCzeta or PKCiota and lambda overexpression attenuates the insulin induced phosphorylation of AKT, and decreases the protein level of IRS1, which suggests a diminished signaling cascade initiated from IRS1 upon insulin treatment (Figs."
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"Resveratrol and 17beta-estradiol significantly inhibited the increase of the blood glucose level and the rise of plasma malondialdehyde in STZ induced diabetic mice, improved the levels of plasma antioxidant capacity and plasma insulin, protected the pancreatic islet cells, and increased the expressions of GLUT4 and IRS-1, but decreased p-ERK expression in skeletal muscle and myocardial tissue."
trips
"Third, concurrent with the decrease in IRS-1 degradation, the inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin also blocked the insulin-stimulated increase in Ser(312) phosphorylation."
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"In glomerular endothelial cells, high glucose inhibited the phosphorylation of Akt, endothelial nitric oxide synthase, and glycogen synthase kinase 3alpha; decreased IRS1 protein expression and increased its association with ubiquitin."
INSR affects IRS1
| 21 1
INSR decreases the amount of IRS1. 1 / 22
| 21 1
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"Therefore, we further revealed that miR-96 targets 3 ' UTRs of INSR and IRS-1 genes directly to suppress the expression of the INSR and IRS-1 protein, resulting in impaired insulin signaling and glycogen synthesis."
IRS1 affects IRS1
| 2 11
IRS1 decreases the amount of IRS1. 7 / 9
| 2 7
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"In the present study, bioinformatics analyses and luciferase assays were employed to show that miR-466 was able to directly target the 3 '-untranslated region of insulin receptor substrate 1 (IRS1) gene, negatively regulating the mRNA and the protein expression levels of IRS1 in OS cells."
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"These data suggest that miR-126 directly targets IRS-1 3 ' UTR and suppresses IRS-1 expression at the posttranscriptional level."
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"Therefore, we further revealed that miR-96 targets 3 ' UTRs of INSR and IRS-1 genes directly to suppress the expression of the INSR and IRS-1 protein, resulting in impaired insulin signaling and glycogen synthesis."
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"Downregulation of IRS-1 by IRS-1 siRNA decreased IRS-1 levels as expected and also the levels of phosphorylated GSK-3beta, which is downstream from IRS-1 in signal transduction."
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"Our results showed that IRS1 short hairpin RNAs can effectively suppress the expression of IRS1, and inhibit the phosphorylation of AKT in IRS1 pathway; reduce the expression of MMP2, MMP3, MMP13, and MMP14, decrease the expression of TNFRSF11B and RANKL (also known as tumor necrosis factor (ligand) superfamily, member 11), however increase the RANKL and TNFRSF11B ratio; decrease cell survival, proliferation, and mineralization, and impair the differentiation of MC3T3-E1 cells."
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"Transfection of IRS-1 siRNA efficiently reduced the level of IRS-1 in three lung cancer cell lines (i.e., A549, H157 and Calu-1) as detected by Western blotting (XREF_FIG A)."
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"Mechanistically, insulin receptor substrate 1 (Irs1) is a direct target of miR-191, and dysregulated IRS1 expression antagonizes STAT5 activation."
Phosphorylated IRS1 decreases the amount of IRS1. 2 / 2
| 2
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"The phosphorylation of IRS-1 promotes IRS-1 degradation and reduces IRS-1 expression, leading to decreased activity of PI3K and Akt."
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"Elevated Ser/Thr IRS-1 phosphorylation may inhibit insulin signalling by (1) downregulating IRS-1 protein levels through ubiquitination [XREF_BIBR - XREF_BIBR], (2) inhibiting the interaction between the tyrosine phosphorylated IR and the phosphotyrosine binding (PTB) domain of IRS-1 [XREF_BIBR - XREF_BIBR], or (3) interfering with the insulin stimulated interaction between IRS-1 and its downstream partner, the phosphatidylinositol 3-kinase (PI3-K) adaptor molecule p85 [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
Modified IRS1 decreases the amount of IRS1. 1 / 1
| 1
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"Moreover, CA-OV3 clones overexpressing IRS-1 were growth inhibited less by ATRA, whereas SK-OV3 clones in which levels of IRS-1 were reduced by expression of antisense IRS-1 became sensitive to growth inhibition by ATRA treatment."
Serine-phosphorylated IRS1 decreases the amount of IRS1. 1 / 1
| 1
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"The phosphorylation of serine in IRS-1 may suppress insulin signaling by downregulating the expression of the IRS1 protein through ubiquitination [XREF_BIBR], thereby inhibiting the interaction between the insulin receptor and IRS1 phosphotyrosine binding domain [XREF_BIBR, XREF_BIBR]."
MIR145 affects IRS1
| 7 5
MIR145 decreases the amount of IRS1. 4 / 11
| 7 4
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"A previous report shows that miR-145 can down-regulate the protein level of IRS1 but can not down-regulate the mRNA of IRS1 XREF_BIBR."
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"Similarly, up-regulation of miR-145 in DFAT cells reduced IRS1 protein expression dramatically, which may decrease expression of adipogenic marker genes in the present study."
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"Further research showed that miR-145 inhibits N-RAS and IRS1 expression to suppress AKT and ERK1/2 activation and VEGF expression in colorectal cancer XREF_BIBR."
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"Though this study discovered that miR-145 inhibited adipogenesis by down-regulated IRS1 gene expression, and IRS1 further affected adipogenic markers expression, which may finally inhibited adipogensis of porcine preadipocytes."
Modified MIR145 decreases the amount of IRS1. 1 / 1
| 1
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"XREF_BIBR has shown that miR-145 overexpression repressed the expression level of IRS-1 and IRS-2 and decreased beta-catenin activity thereby resulting in decreased cell growth."
TGFB affects IRS1
| 11
TGFB decreases the amount of IRS1. 10 / 11
| 11
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"In this model, TGFbeta and Smad3 inhibits IRS-1 expression and activation, which leads to suppression of XIAP and cyclin D1 expression."
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"In addition, TGFbeta treatment decreased the expression and phosphorylation of IRS-1 in CBS-RII cells and the RI inhibitor prevented the inhibitory effect of TGFbeta (XREF_FIG)."
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"This study shows, for the first time, that expression and phosphorylation of IRS-1, an IGF-1R adaptor protein, is decreased by TGFbeta and Smad3 signaling."
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"Our findings further show that TGFbeta and Smad3 inhibits IRS-1 protein expression (Figs XREF_FIG and XREF_FIG) but has little effect on IRS-1 mRNA levels (XREF_FIG), indicating that TGFbeta and Smad3 signaling regulates IRS-1 expression at the post-transcriptional level."
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"TGFbeta signaling inhibits expression and phosphorylation of IRS-1 in colon cancer cells."
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"Further studies showed that TGFbeta signaling suppresses expression and phosphorylation of IRS-1 in colon cancer cells."
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"Further studies are needed to investigate whether TGFbeta and Smad3 regulates Cbl-b expression and/or activity in colon cancer cells and whether Cbl-b is responsible for suppression of IRS-1 expression by TGFbeta and Smad3 signaling."
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"These results demonstrate that TGFbeta suppresses expression and activation of IRS-1 in colon cancer cells."
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"We show for the first time that expression and activation of IRS-1, an IGF-1R adaptor protein, is decreased by TGFbeta and Smad3 signaling."
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"In our study, we show, for the first time, that TGFbeta signaling inhibits IRS-1 expression and activation in colon cancer cells in vitro and in vivo and that upregulated IRS-1 contributes to attenuation of TGFbeta signaling mediated tumor suppressive phenotypes."
SOCS3 affects IRS1
| 1 10
Modified SOCS3 decreases the amount of IRS1. 7 / 7
| 7
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"The results showed that 100nM insulin could induce SOCS3 mRNA expression but not protein expression, and overexpression of SOCS3 decreased IRS1 protein level, insulin stimulated IRS1 tyrosine phosphorylation, PI3K activation, and Akt phosphorylation, but increased IRS1 serine phosphorylation in porcine primary adipocytes."
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"In adipocytes, SOCS3 deficiency increases insulin stimulated IRS1 and IRS2 phosphorylation, whereas the overexpression of SOCS3 reduces both IRS1 protein levels and the phosphorylation of IRS1 and IRS2 [XREF_BIBR]."
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"Consistent with such findings, SOCS3 overexpression decreases the tyrosine phosphorylation levels of IRS1 and inhibits the activity of phosphatidylinositol-3 kinase (PI3K), a downstream signaling element of IRS1, revealing a pivotal role of SOCS3 in insulin resistance."
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"In adipocytes, SOCS3 deficiency increases insulin stimulated IRS1 and IRS2 phosphorylation, whereas overexpression of SOCS3 reduces both IRS1 protein levels and the phosphorylation of IRS1 and IRS2."
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"Overexpression of SOCS3 in adipocytes decreases IRS1 protein levels and subsequent insulin stimulated IRS-1 and -2 phosphorylation, decreases p85 binding to IRS-1, and leads to decreased insulin stimulated glucose uptake in adipocytes."
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"XREF_BIBR Nevertheless, locally, IL-6 induces the expression of SOCS3 in 3T3-L1 adipocytes XREF_BIBR, XREF_BIBR whereas overexpression of SOCS3 in adipocytes reduces IRS-1 protein levels as well as insulin stimulated IRS-1 and IRS-2 phosphorylation and binding of p85 to IRS-1."
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"Overexpression of SOCS1 or SOCS3 in mouse liver or adipose tissue reduced the expression of IRS1 or IRS2 as well as their tyrosine phosphorylation induced by insulin."
SOCS3 decreases the amount of IRS1. 4 / 4
| 1 3
trips
"SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2."
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"The mechanism by which SOCS3 or SOCS1 reduces IRS-1 levels in muscles requires expression of an E3 ubiquitin ligase consisting of Elongin BC and Cullin proteins."
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"As will be described, an increase in SOCS3 reduces the levels of IRS-1 which interferes with insulin stimulated intracellular signaling."
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"Further qPCR data supported that SOCS3 could inhibit the expression of IRS1, LEPR and JAK."
TNF affects IRS1
| 1 9
TNF decreases the amount of IRS1. 9 / 10
| 1 9
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"Our data demonstrated that TNF-alpha significantly reduced levels of glucose consumption and IRS-1 protein expression, while TNF-alpha increased the phosphorylation of IRS-1 Ser307 in adipocytes 24 h after the challenge, suggesting that TNF-alpha induced a condition with the occurrence of insulin resistance."
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"In addition, TNF-alpha has been shown to downregulate the expressions of adiponectin, insulin receptor substrate-1 (IRS-1) and peroxisome proliferator activated receptor gamma (Ppar-gamma) in adipocytes [XREF_BIBR], resulting in elevation of insulin and leptin levels but a decrease of adiponectin [XREF_BIBR, XREF_BIBR]."
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"Both IL-6 and TNF may inhibit the transcription of IRS-1 and glucose transporter (GLUT) -4 genes, thus reducing glucose transport and enhancing insulin resistance in obese patients [XREF_BIBR]."
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"Reportedly, TNF-alpha downregulates IRS-1 and GLUT4 expression in adipose tissue, resulting in insulin resistance in terms of adipocyte glucose uptake."
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"Long-term IL-6 or TNF-alpha treatment inhibits the expression of GLUT4 and IRS-1 in adipose tissue, and in obese patients with T2DM, lower levels of GLUT4 and IRS-1 in VAT were observed."
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"Our results demonstrated that : (1) TNF-alpha triggered IRS-1 phosphorylation on serine 307 and decreased IRS-1 protein level; (2) over-expression of PP4 not only induced IRS-1 phosphorylation and IRS-1 protein reduction, but amplified the effect of TNF-alpha on IRS-1; (3) suppression of PP4 expression and activity restored the effect of TNF-alpha on IRS-1."
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"TNF-alpha and IL-6 can cause insulin resistance by suppressing expression of the insulin receptor substrate -1 (IRS-1) and GLUT-4 though activation of NF- K B pathway [XREF_BIBR, XREF_BIBR]."
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"IL-6 and TNF-alpha can reduce the expression of GLUT4 and IRS-1, and reduce the glucose transport [XREF_BIBR]."
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"XREF_FIG demonstrates that TNF-alpha treatment decreases the transcriptional levels of IRS-1, GLUT4 and adiponectin in a dose dependent manner and treatment with IKK inhibitor shows that the reduced mRNA levels of our genes of interest were restored, confirming that TNF-alpha exerts its effect through the NF-kappaB pathway in adipocytes."
mTORC1 affects IRS1
| 9
MTORC1 decreases the amount of IRS1. 9 / 9
| 9
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"The feedback observed in EGFR and HER2 driven cancers is distinct from a well described feedback mechanism in which mTORC1 inhibition leads to increased IRS-1 expression and up-regulation of IGF-IR and IRS signaling."
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"The continuous activation of mTORC1 in cultured cells suppresses insulin dependent activation of PI3K by downregulating IRS1 (insulin receptor substrate-1) gene expression or by inhibitory phosphorylation of IRS-1."
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"Moreover, inhibition of mTORC1 with either rapamycin or raptor knockdown did not elevate IRS-1 levels, despite potently increasing Akt phosphorylation."
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"Inhibition of mTORC1 with rapamycin has been known to increase IRS-1 levels and induce AKT phosphorylation and downstream signaling [XREF_BIBR]."
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"Direct inhibition of mTORC1 with rapamycin blocks S6Kinase dependent feedback inhibition of IRS-1 expression and activates IGF-1R signaling."
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"AMPK inhibits mTORC1 via raptor or TSC phosphorylations [XREF_BIBR, XREF_BIBR] and supports IRS-1 and Akt expressions."
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"Consistent with previous findings [XREF_BIBR], inhibition of mTORC1 by raptor knockdown or short-term rapamycin treatment slightly enhanced IRS-1 expression."
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"Specifically, mTORC1 impairs PI3K activation in response to growth factors by downregulating the expression of Insulin Receptor Substrate 1 and 2 (IRS-1/2) and Platelet Derived Growth Factor Receptor-Beta (PDGFR-beta) (reviewed in)."
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"Consistent with previous studies demonstrating that chronic mTORC1 activation decreases both the expression and stability of IRS-1 and IRS-2 XREF_BIBR, XREF_BIBR, XREF_BIBR, we find that 24 h treatment with rapamycin increases Irs-1 and Irs-2 transcript levels and IRS-1 protein levels in Tsc2 -/- adipocytes, albeit to levels still significantly lower than Tsc2 +/+ adipocytes (XREF_SUPPLEMENTARY, panels A and B)."
TRIM72 affects IRS1
| 2 7
TRIM72 decreases the amount of IRS1. 6 / 8
| 2 6
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"As evidenced by MyHC immunofluorescence, myogenic index and immunoblotting, MG53 knockout enhanced myogenesis by increasing the level of IRS-1 expression (XREF_FIG)."
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"In contrast, the IRS-1 expression level was decreased about 60% by MG53 but not by C14A or DeltaR in both C2C12 myoblasts and myotubes (XREF_FIG; XREF_SUPPLEMENTARY)."
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"As expected, genetic deletion of MG53 in mice actually ameliorates the development of insulin resistance in skeletal muscles and increases the level of IRS-1, even when the mice are fed a high-fat and high sucrose diet."
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"The genetic disruption of MG53 increases IRS-1 levels, improves insulin signaling in mouse skeletal muscle and ameliorates insulin resistance in diet induced obese (DIO) mice XREF_BIBR, XREF_BIBR."
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"Moreover, MG53 disruption increases IRS-1 protein level in mouse skeletal muscles such as soleus and gastrocnemius-plantaris."
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"The IRS-1 protein level was decreased by MG53 in a concentration dependent manner (XREF_SUPPLEMENTARY) and was restored by the addition of MG132, a proteasome inhibitor (XREF_FIG; XREF_SUPPLEMENTARY)."
Modified TRIM72 decreases the amount of IRS1. 1 / 1
| 1
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"MG53 overexpression decreases IRS-1 protein level in C2C12 myoblasts, and MG53 knockdown increases the IRS-1 protein level in C2C12 myotubes without changing IRbeta and IGFR protein level XREF_BIBR, XREF_BIBR."
MTOR affects IRS1
| 9
MTOR decreases the amount of IRS1. 9 / 9
| 9
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"Loss-of-function and pharmacological inhibition studies have shown that the mTOR target S6K1, for instance, inhibits and desensitizes insulin-PI3K signaling by phosphorylating IRS1 protein and suppressing IRS1 gene transcription."
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"XREF_BIBR The inhibition of mTOR could induce insulin receptor substrate-1 expression to activate AKT."
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"mTOR pathway inhibitors like rapamycin activates such siganling by inducing the expression of insulin receptor substrate-1 (IRS-I), resulting in Akt activation XREF_BIBR."
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"While pre-clinical study demonstrates that prolonged rapamycin treatment suppresses Akt and PKB signaling due to the destabilization of mTORC2 in some types of cultured cancer cells, 172 the results from recent clinical trials provide evidence about PI3K-Akt activation in patient tumors treated with rapamycin or the rapamycin analog RAD001, XREF_BIBR, XREF_BIBR Thus, Dr. Rosen 's group demonstrated that mTOR inhibition with RAD001 treatment induced IRS-1 expression and Akt activation in patient tumors."
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"49 Despite promising clinical results, inhibition of mTOR results in induction of insulin receptor substrate-1 expression, causing a paradoxical Akt activation both in cancer cell lines and in patient tumors treated with mTOR inhibitors."
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"Therefore, mTOR inhibition will increase IRS-1 protein expression, resulting in Akt activation XREF_BIBR."
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"It also has been reported that mTOR inhibition will enhance insulin receptor substrate-1 expression and abrogate feedback inhibition of the pathway, resulting in Akt activation both in cancer cell lines and in patient tumors [XREF_BIBR]."
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"The mTOR active site inhibitor, Torin1, which inhibits mTORC1 and mTORC2, increased IRS-1 levels both during acute and prolonged treatment (XREF_FIG)."
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"We now show that mTOR inhibition induces insulin receptor substrate-1 expression and abrogates feedback inhibition of the pathway, resulting in Akt activation both in cancer cell lines and in patient tumors treated with the rapamycin derivative, RAD001."
IGF1 affects IRS1
| 2 7
IGF1 decreases the amount of IRS1. 6 / 8
| 2 6
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"Indeed, extended IGF-I stimulation for 24 hrs modestly decreased IRS-1 levels in MCF-7 and shPTEN but not MCF-7 and shMM cells."
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"We also showed, in this report, that IRS-1 protein level was decreased by IGF-I stimulation, leading to suppression of IGF-I signal activation."
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"High concentrations of IGF-I decreased levels of IGF-IR and IRS-1 and inhibited the expression and activation of PDGFRalpha."
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"In vivo studies also demonstrated that the direct application of IGF-I to the motoneurons in G93A-SOD1 mouse models activates the PI3K and Akt, p44/42 MAPK and downregulated IGF-IR and IRS-1 expression."
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"Continuous intrathecal administration of IGF-I also decreased levels of IGF-IR and IRS-1, which are up-regulated in the transgenic mice compared to control mice."
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"The reduced IRS-1 protein levels could have been mediated by insulin and IGF -1 resistance, since insulin and IGF-1 regulate IRS gene expression [XREF_BIBR - XREF_BIBR]."
Mutated IGF1 decreases the amount of IRS1. 1 / 1
| 1
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"Interestingly, in contrast to observed effects of GH / IGF-1 mutations, the effect of CR was to decrease Irs1 expression (P = 0.007; analysis of variance; see XREF_TABLE)."
miR-96 affects IRS1
| 4 4
MiR-96 decreases the amount of IRS1. 3 / 7
| 4 3
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"Therefore, this data indicates that miR-96 suppresses the expression of IRS-1 at the post-transcriptional level in L6-GLUT4myc myocytes."
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"Physiologically, miR-96 is strongly induced by fatty acids and downregulates the expression of the insulin receptor (INSR) and the insulin receptor substrate 1 (IRS-1) to induce a failure in insulin signaling and glycogen synthesis in hepatocytes [XREF_BIBR]."
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"As INSR and IRS-1 expression is suppressed at the post-transcriptional level by miR-96 in hepatocytes, this study further examined whether the upregulation of miR-96 causes insulin resistance in hepatocytes."
Modified miR-96 decreases the amount of IRS1. 1 / 1
| 1
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"Accordingly, the overexpression of miR-96 was found to cause a significant decrease in INSR and IRS-1 expression, thereby leading to an impairment of insulin signaling and glycogen synthesis in hepatocytes."
hsa-miR-145-5p affects IRS1
8 |
Transcriptionally active hsa-miR-145-5p decreases the amount of IRS1. 8 / 8
8 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
RPS6KB1 affects IRS1
3 | 5
RPS6KB1 decreases the amount of IRS1. 7 / 7
3 | 4
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"The mechanism behind this may be that suppression of S6K (p70S6K) activity stabilizes IRS-1 and increases IRS-1 adapter protein levels, which in turn induces Akt activity."
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"Similar results were reported in mice, that is, S6K1 mRNA was elevated, thereby inhibiting the expression of IRS-1 by inducing IRS-1 degradation 21."
signor
"In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic target of the CUL7 E3 ligase in a manner that depends on mammalian target of rapamycin and the p70 S6 kinase activities.Elimination of phosphorylation at S307/S312/S527/S636/S639 renders V5-IRS-1 partially resistant to degradation by Fbw8"
signor
"In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic target of the CUL7 E3 ligase in a manner that depends on mammalian target of rapamycin and the p70 S6 kinase activities.Elimination of phosphorylation at S307/S312/S527/S636/S639 renders V5-IRS-1 partially resistant to degradation by Fbw8"
reach
"Loss-of-function and pharmacological inhibition studies have shown that the mTOR target S6K1, for instance, inhibits and desensitizes insulin-PI3K signaling by phosphorylating IRS1 protein and suppressing IRS1 gene transcription."
reach
"These data suggest that the physiological activation of S6K1 does not mediate the decrease of IRS-1 protein level during myoblast differentiation and has no effect on myotube formation."
signor
"In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic target of the CUL7 E3 ligase in a manner that depends on mammalian target of rapamycin and the p70 S6 kinase activities.Elimination of phosphorylation at S307/S312/S527/S636/S639 renders V5-IRS-1 partially resistant to degradation by Fbw8"
Phosphorylated RPS6KB1 decreases the amount of IRS1. 1 / 1
| 1
reach
"They suggested that the enhanced basal phosphorylation of p70S6K, which decreased IRS-1 levels, was the cause of reduced glucose uptake into isolated adipocytes from PTP1B -/- mice and that adipose-PTP1B deletion causes tissue specific insulin resistance."
hsa-miR-126-3p affects IRS1
7 |
Transcriptionally active hsa-miR-126-3p decreases the amount of IRS1. 7 / 7
7 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
glucose affects IRS1
| 7
Glucose decreases the amount of IRS1. 7 / 7
| 7
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"At 1 nM insulin, high glucose reduced IRS1 and IRS2 expression compared with low (P < 0.01 for both)."
reach
"Resveratrol and 17beta-estradiol significantly inhibited the increase of the blood glucose level and the rise of plasma malondialdehyde in STZ induced diabetic mice, improved the levels of plasma antioxidant capacity and plasma insulin, protected the pancreatic islet cells, and increased the expressions of GLUT4 and IRS-1, but decreased p-ERK expression in skeletal muscle and myocardial tissue."
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"IRS-1 levels decreased by 40% in the control glucose clamps (P < 0.005), but did not change during the Intralipid study."
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"Together, these data suggest that glucose induced ERK activation contributes to reduced IRS-1 levels."
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"In human and rodent hepatocytes, high glucose treatment significantly inhibits AKT phosphorylation and IRS-1 expression and subsequently reduces glucose uptake 31, 32."
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"High glucose concentration significantly elevated P-selectin, miR-144 and P2Y12 expression and significantly reduced miR-223 and IRS-1 expression in UT-7 cells."
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"In glomerular endothelial cells, high glucose inhibited phosphorylation of Akt, eNOS and GSK3alpha, decreased IRS1 protein expression and increased association with ubiquitination."
IL6 affects IRS1
| 7
IL6 decreases the amount of IRS1. 7 / 7
| 7
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"In vitro, IL-6 inhibits gene transcription of IRS-1, GLUT4, and PPARgamma and reduces insulin stimulated glucose uptake in 3T3-L1 adipocytes."
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"Both IL-6 and TNF may inhibit the transcription of IRS-1 and glucose transporter (GLUT) -4 genes, thus reducing glucose transport and enhancing insulin resistance in obese patients [XREF_BIBR]."
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"Specifically, IL-6 treatment reduced adiponectin, resistin, glucose transporter type (GLUT)-4, and IRS-1 expression; while TNF-alpha treatment increased secretion of IL-6 and MCP-1 from pre-adipocytes."
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"IL-6 can suppress the expression of IRS-1 and Akt phosphorylation in HepG2 cells XREF_BIBR."
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"TNF-alpha and IL-6 can cause insulin resistance by suppressing expression of the insulin receptor substrate -1 (IRS-1) and GLUT-4 though activation of NF- K B pathway [XREF_BIBR, XREF_BIBR]."
reach
"Long-term IL-6 or TNF-alpha treatment inhibits the expression of GLUT4 and IRS-1 in adipose tissue, and in obese patients with T2DM, lower levels of GLUT4 and IRS-1 in VAT were observed."
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"IL-6 and TNF-alpha can reduce the expression of GLUT4 and IRS-1, and reduce the glucose transport [XREF_BIBR]."
IL1B affects IRS1
| 1 6
IL1B decreases the amount of IRS1. 6 / 7
| 1 6
reach
"IL1beta down-regulates insulin receptor substrate 1 expression, inhibiting insulin induced AKT phosphorylation and glucose uptake in adipocytes [XREF_BIBR]."
reach
"These findings are in agreement with a previous report by Jager et al., in which IL-1beta decreased IRS-1 protein expression and inhibited IRS-1 and Akt signaling in adipocytes, leading to decreased insulin stimulated glucose transport."
reach
"IL-1beta may suppress IRS-1 expression ERK-dependently during transcription and ERK-independently during post-transcription, which may damage insulin signaling [XREF_BIBR]."
reach
"Previous studies, mostly using murine 3T3-L1 adipocytes, have shown that IL-1beta at a very high dose (20 ng/ml) decreased protein expression of IRS-1 and GLUT4 transcripts, and prolonged treatment blunted insulin induced phosphorylation of IRS-1 and Akt."
reach
"These results demonstrate that IL-1beta reduces IRS-1 expression at a transcriptional level through a mechanism that is ERK dependent and at a posttranscriptional level independently of ERK activation."
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"Hence IL-1beta promotes the inhibitory serine phosphorylation, decreases IRS-1 total protein expression, and inhibits insulin stimulated tyrosine phosphorylation of IRS-1."
okadaic acid affects IRS1
| 5
Okadaic acid decreases the amount of IRS1. 5 / 5
| 5
reach
"Meanwhile, OA decreased NF-kappaB protein expression and upregulated IRS1 and GLUT4 protein expression."
reach
"According to the results of XREF_FIG, OA could reduce the expression of NF-kappaB protein and directly increase the expression of IRS1."
reach
"To illustrate the point that OA could relieve the expression of the IRS1 and GLUT4 by blocking the expression of NF-kappaB, PDTC was used to block NF-kappaB in our study."
reach
"Based on the above knowledge, we speculated that OA can relieve insulin resistance by directly affecting the expression of IRS1 protein."
reach
"Moreover, OA reduced the levels of TNF-alpha and IL-6 and upregulated IRS1 and GLUT4 protein expression."
SOCS1 affects IRS1
| 1 4
SOCS1 decreases the amount of IRS1. 3 / 3
| 1 2
reach
"The mechanism by which SOCS3 or SOCS1 reduces IRS-1 levels in muscles requires expression of an E3 ubiquitin ligase consisting of Elongin BC and Cullin proteins."
reach
"Increased levels of SOCS1 in differentiated adipocytes from LP offspring animals suggests that lower IRS1 protein levels in these animals may be at least partly caused by SOCS1 mediated degradation of IRS1."
trips
"SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2."
Modified SOCS1 decreases the amount of IRS1. 2 / 2
| 2
reach
"While the forced expression of SSI-1 reduced the phosphorylation level of insulin receptor substrate 1 (IRS-1), SSI-1 deficiency resulted in sustained phosphorylation of IRS-1 in response to insulin."
reach
"Overexpression of SOCS1 or SOCS3 in mouse liver or adipose tissue reduced the expression of IRS1 or IRS2 as well as their tyrosine phosphorylation induced by insulin."
SMAD3 affects IRS1
| 5
SMAD3 decreases the amount of IRS1. 5 / 5
| 5
reach
"In this model, TGFbeta and Smad3 inhibits IRS-1 expression and activation, which leads to suppression of XIAP and cyclin D1 expression."
reach
"Our findings further show that TGFbeta and Smad3 inhibits IRS-1 protein expression (Figs XREF_FIG and XREF_FIG) but has little effect on IRS-1 mRNA levels (XREF_FIG), indicating that TGFbeta and Smad3 signaling regulates IRS-1 expression at the post-transcriptional level."
reach
"We show for the first time that expression and activation of IRS-1, an IGF-1R adaptor protein, is decreased by TGFbeta and Smad3 signaling."
reach
"This study shows, for the first time, that expression and phosphorylation of IRS-1, an IGF-1R adaptor protein, is decreased by TGFbeta and Smad3 signaling."
reach
"Further studies indicate that TGFbeta and Smad3 suppresses expression and phosphorylation of IRS-1."
IGF1R affects IRS1
| 4 1
IGF1R decreases the amount of IRS1. 1 / 5
| 4 1
reach
"Stimulation of the IGF-IR activates the PI3K/Akt/mTOR cascade and triggers an mTOR dependent decrease in IRS-1 expression and phosphorylation, leading to PI3K/Akt/mTOR inactivation [XREF_BIBR, XREF_BIBR]."
sirolimus affects IRS1
| 1 3
Sirolimus decreases the amount of IRS1. 2 / 3
| 1 2
reach
"These results are in agreement with those of Cerovac et al. in pituitary tumor cells, wherein they demonstrated that octreotide increased the IRS1 phosphorylation level suppressed by rapamycin through SHP1 [XREF_BIBR]."
reach
"Rapamycin inhibits S6K1 dependent IRS-1 serine phosphorylation, increases IRS-1 protein levels, and promotes association of tyrosine phosphorylated IRS-1 with PI3K."
Sirolimus decreases the amount of tyrosine-phosphorylated IRS1. 1 / 1
| 1
reach
"Rapamycin inhibited the inflammatory stress induced p-mTOR and p-S6K expression, reduced the levels of serine phosphorylated IRS-1, and increased total IRS-1 and tyrosine phosphorylated IRS-1 expression (XREF_FIG)."
resveratrol affects IRS1
| 4
Resveratrol decreases the amount of IRS1. 4 / 4
| 4
reach
"Resveratrol suppressed the mRNA expression of c-Src, Rac1, cdc42, IRS-1, MEKK1, MEKK4, and mitogen activated protein kinase along with the protein levels of c-Src, p-Src, and cdc42 in VSMCs."
reach
"Resveratrol treatment decreased the basal levels of IRS-1 and the phosphorylated form of protein kinase B (AKT-P), and resulted in a small increase in insulin stimulated AKT-P (XREF_FIG)."
reach
"Finally, we demonstrate that resveratrol inhibits insulin dependent changes in glucose uptake and glycogen levels and decreases IRS-1 and GLUT4 protein levels, indicating resveratrol represses insulin sensitivity in adipocytes."
reach
"Resveratrol and 17beta-estradiol significantly inhibited the increase of the blood glucose level and the rise of plasma malondialdehyde in STZ induced diabetic mice, improved the levels of plasma antioxidant capacity and plasma insulin, protected the pancreatic islet cells, and increased the expressions of GLUT4 and IRS-1, but decreased p-ERK expression in skeletal muscle and myocardial tissue."
nitric oxide affects IRS1
| 4
Nitric oxide decreases the amount of IRS1. 4 / 4
| 4
reach
"Exogenous nitric oxide inhibits IRS-1 expression in rat hepatocytes and skeletal myocytes."
reach
"Improvement of reduced IRS-1 expression by iNOS deficiency was in agreement with our previous study which showed that iNOS and NO donor reduce IRS-1 expression in cultured skeletal muscle cells, and that iNOS deficiency restored the reduced IRS-1 expression in skeletal muscle of genetically obese, diabetic (ob/ob) mice [XREF_BIBR]."
reach
"In contrast, a selective inducible nitric oxide synthase inhibitor, 1400W, upregulated the expression of IRS-1 protein and the phosphorylation of IRS-1, Akt and PKB, and glycogen synthase kinase-3beta, along with enhanced proliferation and invasion of Panc-1 cells expressing inducible nitric oxide synthase protein."
reach
"In glomerular endothelial cells, high glucose inhibited the phosphorylation of Akt, endothelial nitric oxide synthase, and glycogen synthase kinase 3alpha; decreased IRS1 protein expression and increased its association with ubiquitin."
mTORC2 affects IRS1
| 4
MTORC2 decreases the amount of IRS1. 4 / 4
| 4
reach
"Thus, increased IRS-1 levels upon mTORC2 disruption are not due to enhanced transcription or translation."
reach
"Silencing of mTORC2 components using siRNA (small interfering RNA) also enhanced IRS-1 levels."
reach
"Kim et al. reported that mTORC2 negatively regulates IRS-1 levels by regulating the stability and localization of F-box/WD repeat containing protein 8 (Fbw8), the substrate targeting subunit of the cullin-7 (CUL7) E3 ligase complex [XREF_BIBR]."
reach
"Activation of mTORC2 downregulates the levels of IRS1 via Fbw8."
hsa-miR-8485 affects IRS1
4 |
Transcriptionally active hsa-miR-8485 decreases the amount of IRS1. 4 / 4
4 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
hsa-miR-603 affects IRS1
4 |
Transcriptionally active hsa-miR-603 decreases the amount of IRS1. 4 / 4
4 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
hsa-miR-3941 affects IRS1
4 |
Transcriptionally active hsa-miR-3941 decreases the amount of IRS1. 4 / 4
4 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
hsa-miR-362-3p affects IRS1
4 |
Transcriptionally active hsa-miR-362-3p decreases the amount of IRS1. 4 / 4
4 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
hsa-miR-329-3p affects IRS1
4 |
Transcriptionally active hsa-miR-329-3p decreases the amount of IRS1. 4 / 4
4 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
hexadecanoic acid affects IRS1
| 4
Hexadecanoic acid decreases the amount of IRS1. 4 / 4
| 4
reach
"The upregulation of miR-96 in SFA palmitate treated hepatocytes was recently reported to downregulate IRS-1 expression by binding to its 3 ' UTR regions on mRNA, leading to hepatic insulin resistance XREF_BIBR."
reach
"Expressions of p-IRS-1 and p-AKT were significantly inhibited by palmitate treatment and those effects were dose- dependently attenuated by APL treatment under insulin stimulated conditions (XREF_FIG)."
reach
"We found that palmitic acid can increase the expression of miR-139-5p and reduce IRS1 expression at both the mRNA and protein level."
reach
"This study then examined whether the levels of miR-96, which tentatively targets the 3 ' UTRs of INSR and IRS-1, were increased in the palmitate treated HepG2 cells, because the expression of INSR and IRS-1 was decreased by palmitate."
ethanol affects IRS1
| 4
Ethanol decreases the amount of IRS1. 4 / 4
| 4
reach
"Graphs, together with post hoc Tukey repeated measures tests demonstrated that ethanol significantly reduced the mean expression levels of Insulin R (XREF_FIG) and IRS-1 (XREF_FIG), but increased p70S6K (XREF_FIG) relative to control."
reach
"chronic ethanol intake at 2.5 and 5 xkg (-1) xd (-1) sufficient doses can down-regulate the expression of IRbeta, P-IRbeta, and IRS-1, as well as the phosphorylated forms of IRS-1 and Akt, in rat skeletal muscle, possibly through increased PTP1B activity."
reach
"Chronic ethanol feeding significantly reduced the mean mRNA levels of insulin and IGF-1 polypeptides, insulin, IGF-1, and IGF-2 receptors, IRS-1, and IRS-2 (XREF_FIG)."
reach
"The present study showed that chronic ethanol intake could downregulate the expression levels of IR-beta, IRS-1, and Glut4 in rat cardiac muscles."
dexamethasone affects IRS1
| 1 3
Dexamethasone decreases the amount of IRS1. 3 / 4
| 1 3
reach
"Thus, both insulin and dexamethasone down-regulate IRS-1 expression at the posttranscriptional level; with insulin this is probably due to an effect on protein half-life, whereas with dexamethasone the effect is due to a change in the half-life of IRS-1 mRNA."
reach
"Dexamethasone treatment decreased the expression of insulin receptor substrate 1 (by approximately 40%; P < 0.05) and PKB (by approximately 20%; P < 0.05) in omental but not in s.c. adipocytes."
reach
"As reported previously XREF_BIBR, XREF_BIBR, dexamethasone reduced IRS-1 protein levels."
Nanoparticles affects IRS1
| 4
Nanoparticles decreases the amount of IRS1. 4 / 4
| 4
reach
"As shown in XREF_FIG, the expression level of IRS-1 was significantly reduced by miR-126 NPs compared with control dsRNA NPs."
reach
"We also confirmed that IRS-1 protein levels were reduced by the induction of miR-126 NPs compared with control NPs (XREF_FIG)."
reach
"Thus, miR-126 NPs most likely reduced the levels of IRS-1 through its binding to the IRS-1 3 '-UTR."
reach
"On the other hand, miR-126 NPs reduced IRS-1 levels in rabbit SMCs and reduced the proliferation and migration of VSMCs via the suppression of IRS-1."
JNK affects IRS1
1 | 3
JNK decreases the amount of IRS1. 4 / 4
1 | 3
reach
"To our knowledge, this is the first study to show that increased JNK activation can lead to decreased IRS-1 protein levels, presumably via IRS-1 ubiquitination mediated via serine phosphorylation of this protein."
signor
"Modulation of insulin-stimulated degradation of human insulin receptor substrate-1 by Serine 312 phosphorylationOne of the specific Ser phosphorylation sites in IRS-1 that has been proposed to negatively modulate the insulin signal is Ser312 (numbered according to the human sequence). Prior studies have demonstrated that IRS-1 associates with and is phosphorylated by JNK in vitro on Ser312"
reach
"Combined with the fact that PP4 can not only activate JNK to induce the phosphorylation of IRS-1 on serine 307, but reduce the expression of IRS-1, we believe that PP4 formed a complex with IRS-1 to promote the phosphorylation of IRS-1 via JNK activation as well as reduce the expression of IRS-1."
reach
"Moreover, selective JNK inhibition with JNK-IN-8 or p38 inhibition with SB203580 attenuated the nicotine dependent phosphorylation of Irs1-Ser307 and the subsequent reduction of Irs1 protein expression (XREF_SUPPLEMENTARY)."
AKT affects IRS1
| 2 2
AKT decreases the amount of IRS1. 1 / 3
| 2 1
reach
"In glomerular endothelial cells, high glucose inhibited the phosphorylation of Akt, endothelial nitric oxide synthase, and glycogen synthase kinase 3alpha; decreased IRS1 protein expression and increased its association with ubiquitin."
Phosphorylated AKT decreases the amount of IRS1. 1 / 1
| 1
reach
"However, AKT phosphorylation progressively increased in most cells in time dependent manner (XREF_SUPPLEMENTARY) likely due to the loss of the negative feedback loop between pS6 and insulin receptor substrate 1 (IRS-1) [XREF_BIBR]."
miR-126 affects IRS1
| 3
MiR-126 decreases the amount of IRS1. 3 / 3
| 3
reach
"The knockdown of miR-126 promotes AKT and ERK1/2 activation by upregulating the expression of IRS-1, a target gene of miR-126 [XREF_BIBR]."
reach
"To confirm that IRS-1 is a target gene of miR-126 in hepatocytes, we transfected SK-Hep1 cells with empty plasmid or miR-126 expression plasmid, and investigated whether induction of miR-126 directly represses IRS-1 expression."
reach
"Our findings in hepatocytes reveal a novel mechanism for the development of insulin resistance by providing the first direct evidence that miR-126 mediates the repression of IRS-1 expression in mitochondrial dysfunction."
hsa-miR-5011-5p affects IRS1
3 |
Transcriptionally active hsa-miR-5011-5p decreases the amount of IRS1. 3 / 3
3 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
hsa-miR-4789-5p affects IRS1
3 |
Transcriptionally active hsa-miR-4789-5p decreases the amount of IRS1. 3 / 3
3 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
hsa-miR-4789-3p affects IRS1
3 |
Transcriptionally active hsa-miR-4789-3p decreases the amount of IRS1. 3 / 3
3 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
hsa-miR-190a-3p affects IRS1
3 |
Transcriptionally active hsa-miR-190a-3p decreases the amount of IRS1. 3 / 3
3 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
chromium atom affects IRS1
| 3
Chromium atom decreases the amount of IRS1. 3 / 3
| 3
reach
"Chromium glycinate, acetate and propionate decreased the amount of IRS-1 phosphorylated at serine."
reach
"Chromium glycinate, acetate, and propionate decreased the amount of IRS-1 phosphorylated at serine."
reach
"Compared with model group, chromium malate could significantly promote the secretion levels of GLUT-4, Akt, Irs-1, PPARgamma, PI3K and p38-MAPK, promote AMPKbeta1 phosphorylation, and reduced the level of p-Irs-1 in L6 cells with insulin resistance."
SRC affects IRS1
| 1 2
SRC decreases the amount of IRS1. 1 / 2
| 1 1
reach
"Furthermore, we showed in this study that p/CIP and SRC-1 suppress IRS1 levels to control insulin resistance in different obesity models, which has not been reported before."
Modified SRC decreases the amount of IRS1. 1 / 1
| 1
reach
"These results demonstrate that loss of both p/CIP and SRC-1 increased IRS1 levels and enhanced insulin signaling in the F442A cell line."
PTEN affects IRS1
| 1 2
PTEN decreases the amount of IRS1. 1 / 2
| 1 1
reach
"PTEN down-regulation promoted in turn a reduction of insulin receptor substrate 1 (IRS1) expression."
Modified PTEN decreases the amount of IRS1. 1 / 1
| 1
reach
"Compared to IRS-1 expression upon HCV infection in Huh7.5.1 cells and empty vector group, IRS-1 levels were partially rescued, and pIRS-1 levels were slightly reduced by PTEN overexpression regardless of JFH1 based HCVcc infection."
PRKACA affects IRS1
3 |
PRKACA decreases the amount of IRS1. 3 / 3
3 |
signor
"Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223"
signor
"Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223"
signor
"Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223"
NOS2 affects IRS1
| 3
NOS2 decreases the amount of IRS1. 3 / 3
| 3
reach
"63 In addition, inhibition of iNOS by gene disruption also reversed the decreased IRS-1 expression and thereby improved IRS-1-mediated insulin signaling in skeletal muscle of obese, diabetic (ob/ob) mice."
reach
"These findings indicate that iNOS reduces IRS-1 expression in skeletal muscle via proteasome mediated degradation and thereby may contribute to obesity related insulin resistance."
reach
"Improvement of reduced IRS-1 expression by iNOS deficiency was in agreement with our previous study which showed that iNOS and NO donor reduce IRS-1 expression in cultured skeletal muscle cells, and that iNOS deficiency restored the reduced IRS-1 expression in skeletal muscle of genetically obese, diabetic (ob/ob) mice [XREF_BIBR]."
LSM-36909 affects IRS1
| 3
LSM-36909 decreases the amount of IRS1. 3 / 3
| 3
reach
"Treatment of HepG2 and SMMC-7721 cells with 0.32 microM and 0.64 microM of AFB1 did not decrease IRS1 levels."
reach
"AFB1 also induced a decrease in the levels of IRS1, but an increase in the levels of IRS2 (XREF_FIG)."
reach
"Our current study demonstrates that AFB1 up-regulates IRS2 but down-regulates IRS1 levels in hepatoma cells, leading to a shift in IRS1 and IRS2 expression towards a high IRS2 and IRS1 ratio."
FBXW8 affects IRS1
| 3
Modified FBXW8 decreases the amount of IRS1. 2 / 2
| 2
reach
"Fbw8 overexpression in Sin1 -/- was sufficient to reduce IRS-1 levels in a dose dependent manner."
reach
"The evidence for a physiological role of the Cullin7-Fbw8 E3 ubiquitin ligase includes the report that overexpression of Fbw8 alone or Cullin7-Fbw8 in different cells markedly reduces the steady-state level of IRS-1 and shortens its half-life."
FBXW8 decreases the amount of IRS1. 1 / 1
| 1
reach
"Silencing of Fbw8 increased IRS1 levels."
ESR1 affects IRS1
| 1 2
ESR1 decreases the amount of IRS1. 1 / 2
| 1 1
reach
"Because I3C can stimulate the proteasome mediated degradation of ERalpha that leads to the loss of ERalpha expression, the ablation of ERalpha by I3C is predicted to disrupt estrogen dependent IGF1R and IRS1 gene expression."
Modified ESR1 decreases the amount of IRS1. 1 / 1
| 1
reach
"Because ectopic expression of ERalpha reversed the I3C down-regulation of IGF1R and IRS1 transcript expression, the I3C disruption of ERalpha interactions with the IGF1R and IRS1 promoters mediates the I3C dependent loss of IGF1R and IRS1 gene expression, respectively."
EMP1 affects IRS1
| 3
EMP1 decreases the amount of IRS1. 3 / 3
| 3
reach
"Moreover, TMP could significantly downregulate the expressions of SCAP, SREBP-1c, PAQR3, IRS-1, PI3K, Akt, and mTORC1 (P < 0.01)."
reach
"TMP Downregulates the Protein Expressions of IRS-1, PI3K, p-Akt, and mTORC1 in Adipose Tissues."
reach
"This study showed that TMP can downregulate the protein expressions of IRS-1, PI3K, p-Akt, and mTORC1 in adipose tissues."
EDN1 affects IRS1
| 1 2
EDN1 decreases the amount of IRS1. 2 / 3
| 1 2
reach
"IRS-1 protein levels were similarly decreased by ET-1 and 8-bromo cAMP, attributable to suppressed mRNA expression."
reach
"ET-1 decreased the expression of insulin receptor, insulin receptor substrate-1 and phosphodiesterase-3B and increased the expression of endothelin receptor-B (ET (B) R) in visceral but not in subcutaneous adipocytes."
Aldosterone affects IRS1
| 3
Aldosterone decreases the amount of IRS1. 3 / 3
| 3
reach
"Aldosterone induces insulin resistance in isolated vascular smooth muscle cells (VSMC) by reducing IRS1 expression and downstream Akt signaling."
reach
"XREF_BIBR Aldosterone decreases IRS-1 expression and suppresses insulin signaling, XREF_BIBR and clinical reports have indicated that patients with primary aldosteronism commonly have impaired glucose tolerance."
reach
"Aldosterone (1-100 nmol/L) dose-dependently decreased insulin receptor substrate-1 protein expression with a peak at 18 hours (n = 4)."
AGT affects IRS1
| 3
AGT decreases the amount of IRS1. 3 / 3
| 3
reach
"Thus, angiotensin II decreases IRS-1 protein levels in VSMCs via Src, PDK1, and reactive oxygen species mediated phosphorylation of IRS-1 on Ser307 and subsequent proteasome dependent degradation."
reach
"AngII also decreases IRS-1 protein levels in vascular smooth muscle cells and induces SOCS-3 (suppressor of cytokine signalling-3), which further inhibits insulin signalling and insulin stimulated glucose disposal [XREF_BIBR, XREF_BIBR]."
reach
"We previously demonstrated that Ang II decreases IRS-1 protein expression, and consequently attenuates glucose metabolism mediated via the phosphatidylinositol 3 kinase-Akt signaling pathway."
tamoxifen affects IRS1
| 2
Tamoxifen decreases the amount of IRS1. 2 / 2
| 2
reach
"Furthermore, both tamoxifen and ICI 182,780 decreased total IRS1 levels and reduced both basal and IGF-1-induced tyrosine phosphorylation of IRS1 [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
reach
"In estrogen sensitive breast cancer cell lines, tamoxifen treatment reduces IRS-1 expression and function; consequently, inhibiting IRS-1 and PI-3K signaling."
simvastatin affects IRS1
| 2
Simvastatin decreases the amount of IRS1. 2 / 2
| 2
reach
"Finally, statin administration decreases TAZ, IRS1 level and insulin sensitivity."
reach
"Simvastatin suppressed the phosphorylation of IR, IRS-1 and Akt, and total expression of IR or IRS-1, but did not affect Akt."
peroxynitrite affects IRS1
| 2
Peroxynitrite decreases the amount of IRS1. 2 / 2
| 2
reach
"Our results suggest that peroxynitrite reduces the IRS-1 protein level and decreases phosphorylation of IRS-1 concurrent with nitration of its tyrosine residues."
reach
"Thus, peroxynitrite reduces the level of IRS-1, while inducing at the same time its tyrosine nitration, thereby impairing insulin signalling on Akt and PKB."
p38 affects IRS1
| 2
P38 decreases the amount of IRS1. 2 / 2
| 2
reach
"However, p38 inhibition did not prevent the loss of IRS-1 protein levels or insulin signaling to PKB in insulin resistant cells."
reach
"In the presence of insulin and the oxidant, the inhibition of p38 MAPK increased IRS-1 protein expression by 41% (p < 0.05) (XREF_FIG, left panel), thereby preventing 29% of the oxidant stress induced loss of IRS-1."
miR-628 affects IRS1
| 2
Modified miR-628 decreases the amount of IRS1. 2 / 2
| 2
reach
"Our results also showed that IRS1 protein levels were decreased after burn injury and that miR-628 overexpression in both L6 myoblasts and rats significantly decreased IRS1 expression."
reach
"Our results indicate that miR-628 overexpression after burn injury enhances FoxO3a activation by repressing IRS1 protein expression, promotes skeletal cell apoptosis and ultimately induces skeletal muscle atrophy."
miR-497 affects IRS1
| 2
MiR-497 decreases the amount of IRS1. 2 / 2
| 2
reach
"However, in the mutant group, no detectable change in luciferase activity was observed (XREF_FIG), suggesting that miR-497 suppressed the transcription of the IRS1 gene by targeting the putative 3 ' UTR of IRS1 mRNA independently."
reach
"Total proteins from representative tumor samples were analyzed by western blotting, and the results demonstrated that miR-497 suppressed the expression of IRS1 and p-AKT, as well as p-ERK1/2, in vivo (XREF_FIG)."
miR-432 affects IRS1
| 2
Modified miR-432 decreases the amount of IRS1. 2 / 2
| 2
reach
"It was obvious that the overexpression of miR-432 reduced the expression of IGF2, IRS1, PI3K, PDK1, and AKT at mRNA and protein levels, but circTTN overexpression alleviated these effects (XREF_FIG C)."
reach
"Furthermore, overexpression of miR-432 significantly inhibited the expression of IGF2, IRS1, PI3K, PDK1, and AKT, but these effects were abolished by increased circTTN."
miR-17 affects IRS1
| 2
Modified miR-17 decreases the amount of IRS1. 2 / 2
| 2
reach
"In summary, we found that transgenic expression of miR-17 increased mouse lifespan by repressing expression of IRS1 and ADCY5."
reach
"22 In this study, we found that transgenic expression of miR-17 increased mouse lifespan by repressing expression of insulin receptor substrate 1 (IRS1) and ADCY5."
miR-139-5p affects IRS1
| 2
Modified miR-139-5p decreases the amount of IRS1. 1 / 1
| 1
reach
"In conclusion, our study confirmed that 1) elevated levels of miR-139-5p in the pancreatic tissues of diabetic rats can suppress IRS1 gene expression to promote cell apoptosis, and 2) liraglutide has anti-apoptotic effects by downregulating miR-139-5p levels and upregulating IRS1 gene expression."
MiR-139-5p decreases the amount of IRS1. 1 / 1
| 1
reach
"Mechanistically, we demonstrated that miR-139-5p specifically suppressed IRS1 expression."
miR-128 affects IRS1
| 2
Modified miR-128 decreases the amount of IRS1. 1 / 1
| 1
reach
"Western blot analysis indicated that the overexpression of miR-128 significantly downregulated IRS1 expression and its downstream Akt signaling in CRCcells."
MiR-128 decreases the amount of IRS1. 1 / 1
| 1
reach
"Collectively, our study provides evidence that miR-128 targeted and negatively regulated IRS1 expression, whereby the functional injury of CMECs induced by Hcy was ameliorated."
miR-1225-5p affects IRS1
| 2
MiR-1225-5p decreases the amount of IRS1. 1 / 1
| 1
reach
"In addition, considering that overexpression of miR-1225 decreased both mRNA and protein level of beta-catenin (data not shown) together with the finding that miR-1225-5p could decrease the expression of IRS1, one may speculate that miR-1225-5p was able to transcriptionally downregulate beta-catenin through decreasing the expression of IRS1."
Modified miR-1225-5p decreases the amount of IRS1. 1 / 1
| 1
reach
"We found that miR-1225-5p could directly bind the 3 '-UTR of IRS1 and over-expression of miR-1225-5p downregulated IRS1 expression in both mRNA and protein level."
isotretinoin affects IRS1
| 2
Isotretinoin decreases the amount of IRS1. 2 / 2
| 2
reach
"IRS-1 expression is negatively regulated by all-trans retinoic acid (ATRA), which arrests the growth of ovarian carcinoma cells in G 0 -G 1 [XREF_BIBR]."
reach
"We found that all-trans retinoic acid (RA) decreases IRS-1 protein levels in MCF-7, T47-D, and ZR75.1 breast cancer cells, which are growth arrested by RA, but not in the RA resistant MDA-MB-231 and MDA-MB-468 cells."
hsa-miR-5580-3p affects IRS1
2 |
Transcriptionally active hsa-miR-5580-3p decreases the amount of IRS1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
hsa-miR-511-3p affects IRS1
2 |
Transcriptionally active hsa-miR-511-3p decreases the amount of IRS1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
hsa-miR-223-5p affects IRS1
2 |
Transcriptionally active hsa-miR-223-5p decreases the amount of IRS1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
hsa-miR-1277-5p affects IRS1
2 |
Transcriptionally active hsa-miR-1277-5p decreases the amount of IRS1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
hsa-miR-1185-2-3p affects IRS1
2 |
Transcriptionally active hsa-miR-1185-2-3p decreases the amount of IRS1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
hsa-miR-1185-1-3p affects IRS1
2 |
Transcriptionally active hsa-miR-1185-1-3p decreases the amount of IRS1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
hsa-let-7f-2-3p affects IRS1
2 |
Transcriptionally active hsa-let-7f-2-3p decreases the amount of IRS1. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
biopax:mirtarbase
No evidence text available
arachidonic acid affects IRS1
| 2
Arachidonic acid decreases the amount of IRS1. 2 / 2
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reach
"A branched-chain AA mixture decreased IRS-1 and FASN expression."
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"In proliferating C2C12 cultures, AA led to lower mRNA expression of insulin-R, GLUT1, and IRS-1."
all-trans-retinoic acid affects IRS1
| 1 1
All-trans-retinoic acid decreases the amount of IRS1. 1 / 2
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reach
"Studies to determine the mechanism by which ATRA reduced IRS-1 expression showed that ATRA altered steady-state levels of IRS-1 mRNA and the stability of IRS-1 protein."
aldosterone affects IRS1
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Aldosterone decreases the amount of IRS1. 2 / 2
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reach
"These data indicate that aldosterone decreases insulin receptor substrate-1 expression via Src and reactive oxygen species stimulation by proteasome dependent degradation in vascular smooth muscle cells; thus, aldosterone may be involved in the pathogenesis of vascular insulin resistance via oxidative stress."
reach
"In addition, in rat vascular smooth muscle cells, aldosterone downregulated IRS-1 expression via stimulating the production of ROS, an effect which was markedly attenuated by treatment with the selective mineralocorticoid receptor antagonist eplerenone [XREF_BIBR]."
X affects IRS1
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X decreases the amount of IRS1. 2 / 2
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"In order to determine whether HBx induced SOCS3 expressions result in the reduction of IRS1 protein levels, we cotransfected the SOCS3 expression vector into HBx-stable cell lines."
reach
"The transient transfection of HBx into HepG2 cells induced a significant suppression of protein levels of IRS1 in a dose dependent manner."
UGCG affects IRS1
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UGCG decreases the amount of IRS1. 2 / 2
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reach
"In skeletal muscle, GCs were shown to cause IR by reducing transcription of IRS1, while increasing expression of proteins that interfere with insulin action, including protein tyrosine phosphatase type 1B, leukocyte common antigen related protein (LAR) and p38MAPK."
reach
"Their experiment also showed that GCs could reduce the expression of IRS-1, which would also contribute to desensitization of the skeletal muscle tissue towards the actions of insulin."
TNS2 affects IRS1
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TNS2 decreases the amount of IRS1. 2 / 2
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"C1-Ten reduces IRS-1 protein levels via its PTPase activity 3."
reach
"Silencing of TNS2 markedly increased the activated forms of IRS1 (human pS616, pY612, or mouse pS612, pY608), Akt (pS473), Mek (pS217/221), and Erk (pT202 and pY204), as well as IRS1 protein levels, suggesting that TNS2 negatively regulated these pathways."
ST3GAL4 affects IRS1
| 2
ST3GAL4 decreases the amount of IRS1. 2 / 2
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"i.c. STZ treatments caused neurodegeneration with increased pTau, AbetaPP, Abeta 42, ubiquitin, and SNAP-25, and reduced levels of synaptophysin, IGF-1 receptor (R), IRS-1, Akt, p70S6K, mTOR, and S9 -GSK-3beta."
reach
"In contrast, i.c. STZ inhibition of IRS-1 protein expression was abrogated by both early and delayed administration of T3D-959 (XREF_FIG)."
SREBP-1c affects IRS1
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SREBP-1c decreases the amount of IRS1. 2 / 2
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"SREBP-1c may suppress IRS-1 expression and the subsequent insulin signaling pathway."
reach
"SREBP-1c overproduction decreased Irs-1 mRNA and IRS-1 protein expression in a dose dependent manner, and suppressed the resultant insulin signalling, whereas SERBP-1c knockdown by Serbp-1c siRNA blocked the downregulation of IRS-1 induced by PA.."
Proteasome affects IRS1
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Proteasome decreases the amount of IRS1. 1 / 2
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reach
"Ubiquitin content of IRS-1 is increased in the presence of IGF-I, and inhibitors of the proteasome prevented the reduction of IRS-1 levels seen following IGF-I exposure."
PRKCZ affects IRS1
1 | 1
PRKCZ decreases the amount of IRS1. 1 / 2
1 | 1
signor
"Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223"
NFkappaB affects IRS1
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NFkappaB decreases the amount of IRS1. 2 / 2
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reach
"As the important target of the inflammatory pathways, NF-kappaB could disrupt IRS1 and downregulate the expression of IRS1 under conditions of insulin resistance [XREF_BIBR, XREF_BIBR]."
reach
"NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells), one of the important inflammatory pathways, can decrease the expression of insulin receptor substrate 1 (IRS1) in patients with IR [XREF_BIBR]."
NCOA3 affects IRS1
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Modified NCOA3 decreases the amount of IRS1. 1 / 1
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reach
"These results demonstrate that loss of both p/CIP and SRC-1 increased IRS1 levels and enhanced insulin signaling in the F442A cell line."
NCOA3 decreases the amount of IRS1. 1 / 1
| 1
reach
"Furthermore, we showed in this study that p/CIP and SRC-1 suppress IRS1 levels to control insulin resistance in different obesity models, which has not been reported before."
MIR7-1 affects IRS1
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Modified MIR7-1 decreases the amount of IRS1. 2 / 2
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reach
"Further studies showed that over-expression of miR-7 down-regulated insulin receptor substrate 1 (IRS1) expression as well as inhibited insulin stimulated Akt phosphorylation and glucose uptake."
reach
"Similarly, in another cellular IR model (C2C12 myoblasts pretreated with fatty acids), overexpression of miR-7 downregulates IRS-1 expression via a direct interaction through binding to its 3 '-UTR [XREF_BIBR]."
Insulin Resistance affects IRS1
| 1 1
Insulin Resistance decreases the amount of IRS1. 1 / 2
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reach
"Decreased expression of Irs-1, Akt2 and Glut4, all key components of the insulin signaling pathway, results in reduced insulin action and IR."
IRS2 affects IRS1
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Modified IRS2 decreases the amount of IRS1. 2 / 2
| 2
reach
"(4) The gene expression of IRS-1 in muscle was significantly decreased by 87.7% in FFA group, and the expression of IRS-2 was decreased by 50.7% (all P < 0.05)."
reach
"(4) The gene expression of IRS-1 was significantly decreased by 42.3% in HF group (P < 0.05), and the expressions of IRS-2 and Glut-2 were decreased by 28.1% and 22.9% (P < 0.05) compared with NC group."
HG affects IRS1
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HG decreases the amount of IRS1. 2 / 2
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"Concomitantly with the HG induced decrease of IRS-1 protein levels in HGEC, we noted increased Ser636 phosphorylation and reduced Tyr465 phosphorylation of the existing levels of IRS1; suggesting that the activation response of IRS-1 Tyr465 phosphorylation is diminished in HG treated cells."
reach
"To evaluate the contribution of impaired synthesis versus enhanced degradation to HG induced reduction of IRS1 protein levels, CHO/IR cells were coincubated with HG and cycloheximide, a protein translation inhibitor, for 14 h. Without cycloheximide, the reduction in IRS1 protein levels by HG was not detectable after 14 h of exposure (XREF_FIG, lane b versus lane a)."
GSK3B affects IRS1
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Modified mutated GSK3B decreases the amount of IRS1. 1 / 1
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reach
"Overexpression of the constitutively active GSK3beta mutant significantly reduced IRS1 protein levels (XREF_FIG, lane c versus lane a), whereas overexpression of the kinase deficient mutant slightly increased the level of IRS1 protein (XREF_FIG, lane b versus lane a)."
GSK3B decreases the amount of IRS1. 1 / 1
| 1
reach
"Further support for the hypothesis that reduced GSK-3beta activity in beta-Gsk-3beta -/- mice can increase IRS1 and IRS2 levels and insulin signalling was obtained by in vitro experiments with a potent and selective inhibitor of GSK-3 activity, SB216763 [XREF_BIBR]."
FOXC1 affects IRS1