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INS decreases the amount of IRS1. 57 / 70
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"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."

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"Here we report that insulin suppressed the expression of both IRS-1 and IRS-2 proteins in Fao hepatoma cells."

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"As shown in XREF_FIG, the insulin signaling was rapidly activated by physiological concentration of insulin (10 -7 mol/l) in untreated cells, evidenced by increased levels of p-IRbeta (Tyr1361), p-IRS-1 (Tyr896) and p-Akt, and decreased level of p-IRS-1 (Ser307)."

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"Regarding the upstream components of the pathway, the sources of significant variance detected by two-way ANOVA tests were due to similarly elevated levels of insulin receptors (Figure 5A), IGF-1 receptors (Figure 5D), and p/T IRS-1 (Figure 5I), and reduced expression of pY-Insulin receptors (Figure 5B), p/T Insulin (Figure 5C) and IGF-1 (Figure 5F) receptors, and IRS-1 (Figure 5G) in CS and ES relative to CC and/or EC."

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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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"Overexpression of miR-7 downregulated the expression of insulin receptor substrate 1 as well as inhibited insulin-stimulated Akt phosphorylation and glucose uptake."

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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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"Pioglitazone prevents THF-alpha-induced insulin resistance by restoring TNF-alpha-reduced insulin stimulated 2-deoxyglucose uptake, tyrosine phosphorylation, and protein levels of insulin receptor and IRS-1."

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"Adenoviral knockdown of miR-27a in HF+ miR-27a (-) mice increased insulin stimulated p-IRS-1 and p-Akt protein expressions compared to HF+ EV mice."

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"For example, TF exposure can attenuate insulin signal transduction via especially down-regulating insulin receptor substrate-1 (IRS-1) levels, while, simultaneously, it can imitate the binding of corticosterone to the GR and enhance insulin induced lipogenesis."

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"The present data revealed that insulin + GJG treatment inhibits the increased IRS-1 tyrosine phosphorylation levels (XREF_FIG); therefore, these improvements are thought to improve the abnormal activation of PI 3-kinase resulting in the correction of decreased efficiency of glucose metabolization."

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"In addition, high insulin concentrations decreased miR-145 expression, regulated IRS-1 protein expression, and promoted cell proliferation [79]."

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"In our previous study, we observed that 10 M insulin significantly promoted INSR phosphorylation and IRS1 protein expression at 2 h in alveolar bone marrow MSCs, and obviously inhibited INSR phosphorylation and IRS1 protein expression by day 7, despite this, the treatment particularly enhanced cell proliferation and osteogenic differentiation [48]."

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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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"The hyperactivation of mTORC1 by nutrient excess (amino acids, lipids, obesity) has been implicated in decreased insulin signal transduction at the level of IRS1."

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"Both miR-143 and miR-145 have been recently reported to further interfere with insulin signaling by reducing IRS1 levels in mouse aortic smooth muscle cells [33]."
| PMC

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"Our results showed that 10 M insulin significantly reduced the protein levels of INSR (P  < 0.001), IGF1R (P  < 0.001), and IRS1 (P  < 0.001) in human DPSCs."

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"In contrast, the prolonged treatment of adipocytes with insulin reduces the level of IRS1 through a proteasome-dependent process."

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"IL-1β also was lifted in serum by styrene, which can cause dysregulation in insulin signaling by suppressing IRS-1 expression both dependent and independent on ERKs pathway during transcription and po[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"In contrast, Chen et al. [13] have shown that Ucn2 knockout animals were more sensitive to insulin when compared to wild animals and in vitro studies [13,80] have reported that Ucn2 decreased the phosphorylation levels of Akt (Ser ), IRS-1 (Tyr ), and ERK1/2 (Thr /Tyr ) in differentiated muscle cells incubated with insulin."

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"IL1beta down-regulates insulin receptor substrate 1 expression, inhibiting insulin induced AKT phosphorylation and glucose uptake in adipocytes [XREF_BIBR]."

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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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"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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"The addition of 300 μm PA significantly inhibited insulin-induced [3 H]-2-deoxyglucose uptake and reduced the expression of IRS-1 and GLUT4, which indicates that PA treatment induced IR in SVOG cells.[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Defects in virtually all of the mentioned signalling parameters have been demonstrated in subjects with overt T2D, but the results are very diverging and many studies could not demonstrate these defec[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"In contrast, whereas in group E2 insulin resistance throughout the hormonal treatment was related to diminished expression and phosphorylation of IRS-1, in group E the decrease in insulin sensitivity between days 11 and 16 of treatment was not related to a decrease in IRS-1 expression."

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"Insulin stimulated tyrosine phosphorylation of the insulin receptor beta-subunit and insulin receptor substrate-1 (IRS-1) in intact skeletal muscle of SHROB was reduced by 36 and 23%, respectively, compared with SHR, due primarily to 32 and 60% decreases in insulin receptor and IRS-1 protein expression, respectively."

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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]."

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"The combined treatment of insulin and selenium may decrease blood glucose by upregulating IRS-1, PI3K and GLUT4 levels in skeletal muscles of diabetic rats."

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"Moreover, the insulin signaling pathway was disordered in the livers (see XREF_SUPPLEMENTARY), characterized by increased IRS-1 (serine 307) and JNK phosphorylation, reduced IRS-1 expression and AKT and GSK3beta phosphorylation."

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"Treatment of HIRc-B cells with insulin for 6 h decreases the expression of IRS-1 but does not decrease the expression of IRS-2 [35] ."

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"Insulin (1 p M) treatment decreased the amount of IRS-1 in cells ti 600 in 4 h."

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"The results of western blot revealed that insulin treatment increased Ser307 phosphorylation of IRS1, but decreased the levels of p-IRS1 (Tyr632) and p-Akt in FFA-stimulated HepG2 cells in comparison [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"XREF_BIBR, early insulin therapy reduced c-Jun N-terminal kinase and IRS-1 expression; it also improved ER stress and steatosis in the rat liver."

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"Investigating the insulin effect on transcription and cytokine production by CD4+ cells, we found that insulin suppressed IRS1, PIK3CG, STAT5A, and ABL1 mRNA levels (Figure 2G), promoting a decrease in insulin sensitivity."

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"These results suggest that miR-222 from the HFD-gWAT-exosomes suppresses insulin signaling pathway by suppressing IRS1 protein expression."

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"Interestingly, insulin exposure significantly reduced IRS-1 protein levels in 0.25 mM OA, but not in control or 1.0 mM OA, treated cells."

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"Chronic insulin treatment significantly decreased IRS1 expression ( Fig. 2 E)."

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"Peripherally, IL-6 impairs insulin action via down-regulating the insulin receptor substrate 1 (IRS-1) expression [ 100 ] and inducing the expression of SOCS-3 [ 102 ]."

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"For instance, chronic insulin treatment reduces not only INSR and GLUT4 expression in adipocytes (Thomson et al., 1997; Srivastava et al., 2018) and muscle cells (Yang et al., 2012; Turner et al., 2018) but also INSR and IRS1 expression in hepatoma cells (Yuan et al., 2002)."

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"Prolonged insulin stimulation reduced IRS-1 levels in WT but not in SIN1 -/- (XREF_FIG)."

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"Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression."

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"In diabetic mice, upregulated HDAC6 expression in skeletal muscle impairs insulin signaling by downregulating insulin receptor substrate-1 (IRS1) levels ( Kumar and Datta, 2022 )."

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"Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression."

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"136 A linear regression analysis has suggested that TSH is also independently and positively associated with HOMA-IR.137 Moreover, recent in vitro studies in mice have reported that TSH stimulates nuclear factor-kappa B (NF-κB) DNA-binding activity via the CAMP-PKA-dependent pathway to increase TNF-α transcriptional activity.138,139 The possible mechanisms by which TNF-α impairs insulin signal transduction include downregulating the expression of IRS-1, inhibiting tyrosine phosphorylation of IRS-1, and increasing serine/threonine phosphorylation of IRS-1."

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"AME supplementation reduced levels of FBG, HbA1c, HOMA-IR and hepatic lipid profiles as well as enhanced insulin signaling by increased the protein levels of IRS-1 accompanied GLUT2 in diabetic mice."

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"Furthermore, the suppressed insulin-stimulated AKT phosphorylation was closely associated with impaired insulin-stimulated phosphorylation levels of IRS1 and its upstream IR (Figures 2A,B,D)."

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"TNF-α and IL-6 can also trigger IR by inhibiting certain insulin signalling pathways involved in suppressing insulin signal transduction by serine phosphorylation of IRS1 and activation of JAK-STAT signalling pathway, causing a decrease in GLUT4 and IRS1 expression."

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"In vitro, the incorporation of miR-27a-enriched Ad-EVs in recipient SkM cells reduces the insulin-stimulated phosphorylation of IR-1 and AKT and reduces the mRNA levels of PPARα, IRS-1, and GLUT4 in muscle cells."

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"Some of the studies suggest that insulin also down-regulates the expression of IRS-1 [6,14], however, it did not affect the IRS-1 expression in 3T3-L1 preadipocytes and mouse embryo fibroblasts [35]."

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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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"However, treatment of insulin-resistant HepG2 cells with HM-chromanone decreased the phosphorylation level of IRS1 Ser307 residue in a concentration-dependent manner."

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"Insulin (I p M) treatment decreased the amount of IRS-1 in the cells - 60% in 4 h. BAPTA-AM (200 u M) totally abolished the insulin induced downregulation of IRS-1."

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"In line with this, the insulin decreased mRNA expression of IRS1 and IRS2 in skeletal muscle of type 2 diabetic patients [65, 66]."

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"Insulin (1 u M) treatment decreased the amount of IRS-1 in these transiently permeabilized cells - 50% in 4 h."

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"In addition, as shown in Fig. 3B-E, insulin stimulation increased the transcript levels of IRS1 and GLUT1 by 1- and 2-fold in the NC group, but decreased the levels of IRS1 by 58%, with no change in GLUT1 in the HepG2/PTP1B cells."

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"Resistin also diminished insulin stimulated IRS-1 tyrosine phosphorylation levels without affecting its protein content."