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IRS1 — TNF

Pathways - manually collected, often from reviews:

• OpenBEL Selventa BEL large corpus: IRS1 → TNF (increases)
  Evidence: tumour necrosis factor alpha (TNFalpha) and chronic hyperinsulinemia two inducers of insulin resistance trigger increased S/T phosphorylation of IRS-1 and IRS-2
• OpenBEL Selventa BEL large corpus: IRS1 → TNF (decreases)
  Evidence: adipose tissue produces a pro-inflammatory cytokine, tumour necrosis factor alpha, which can inhibit insulin signalling by inhibiting the phosphorylation of the insulin receptor and IRS-1.19
• OpenBEL Selventa BEL large corpus: IRS1 → TNF (decreases)
  Evidence: In addition, TNF-a activates the JNK pathway, mediating an increased serine phosphorylation of IRS-1 and reducing insulin- stimulated tyrosine phosphorylation of IRS-1

Text-mined interactions from Literome

Miura et al., Biochim Biophys Acta 1999 (Insulin Resistance) : We have examined the effect of TNF-alpha on insulin induced glucose uptake and activations of tyrosine kinase, IRS-1 , PI3K and PKC in rat adipocytes
Engelman et al., Mol Endocrinol 2000 (Insulin Resistance) : However, little is known about which signaling molecules are involved in this process in adipocytes and about the temporal sequence of events that ultimately leads to TNFalpha stimulated IRS-1 serine phosphorylation ... Additional experiments show that MEK1/2 activity is required for TNFalpha induced IRS-1 serine phosphorylation, thereby suggesting a mechanism by which these inhibitors restore insulin signaling ... We observe that TNFalpha requires 2.5-4 h to markedly reduce insulin triggered tyrosine phosphorylation of IRS-1 in 3T3-L1 adipocytes
Rui et al., J Clin Invest 2001 (Insulin Resistance) : Insulin/IGF-1 and TNF-alpha stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways ... This antibody revealed that TNF-alpha , IGF-1, or insulin stimulated phosphorylation of IRS-1 at Ser307 in 3T3-L1 preadipocytes and adipocytes
Ozes et al., Proc Natl Acad Sci U S A 2001 (Insulin Resistance) : Tumor necrosis factor (TNF) inhibited insulin promoted tyrosine phosphorylation of IRS-1 and activated the Akt/protein kinase B serine-threonine kinase, a downstream target for phosphatidylinositol 3-kinase ( PI 3-kinase ) ... The effect of TNF on insulin promoted tyrosine phosphorylation of IRS-1 was blocked by inhibition of PI 3-kinase and the PTEN tumor suppressor, which dephosphorylates the lipids that mediate PI 3-kinase functions, whereas constitutively active Akt impaired insulin promoted IRS-1 tyrosine phosphorylation ... Conversely, TNF inhibition of IRS-1 tyrosine phosphorylation was blocked by kinase dead Akt
Takeshita et al., J Inorg Biochem 2001 (Diabetes Mellitus, Type 2...) : Overall, the present study demonstrates that VO ( opt ) ( 2 ) exerts an anti-diabetic effect in ob/ob mice by ameliorating impaired glucose tolerance, and furthermore, attenuates the TNF-alpha induced decrease in IRS-1 phosphorylation in adipocytes
Goetze et al., Biochem Biophys Res Commun 2001 : TNFalpha had no effect on insulin induced tyrosine-phosphorylation of IR or IRS-1, but inhibited insulin stimulated IRS-1/PI3K-association by 84 %
Tagami et al., J Biol Chem 2002 (Insulin Resistance) : Pharmacological depletion of GM3 in adipocytes by an inhibitor of glucosylceramide synthase prevented the TNF-alpha induced defect in insulin dependent tyrosine phosphorylation of IRS-1 and also counteracted the TNF-alpha induced serine phosphorylation of IRS-1
Zamorano et al., Int Immunol 2001 : Moreover, TNF-alpha had no effect on the activation of IRS-1 induced by IL-4
Maeda et al., Nat Med 2002 (Insulin Resistance) : Our results indicate that adiponectin/ACRP30 deficiency and high TNF-alpha levels in KO mice reduced muscle FATP-1 mRNA and IRS-1 mediated insulin signaling, resulting in severe diet induced insulin resistance
Gao et al., J Biol Chem 2002 : In this study, using phosphospecific antibodies against rat IRS-1 phosphorylated at Ser ( 307 ) ( equivalent to Ser ( 312 ) in human IRS-1 ), we observed serine phosphorylation of IRS-1 in response to TNF-alpha or calyculin A treatment that paralleled surrogate markers for IKK activation
Jiang et al., J Biol Chem 2003 (Insulin Resistance) : Salicylic acid reverses phorbol 12-myristate-13-acetate ( PMA ) - and tumor necrosis factor alpha (TNFalpha) induced insulin receptor substrate 1 (IRS1) serine 307 phosphorylation and insulin resistance in human embryonic kidney 293 (HEK293) cells ... The results showed that both PMA and TNFalpha inhibited insulin induced Akt phosphorylation and promoted IRS1 phosphorylation on Ser-307 ... Salicylic acid pretreatment completely reversed the effects of PMA and TNFalpha on both Akt and IRS1 ... SP600125, a JNK inhibitor, prevented PMA and TNFalpha induced IRS1 Ser-307 phosphorylation
Gao et al., J Biol Chem 2003 (Insulin Resistance) : Taken together, these data suggest that serine phosphorylation of IRS-1 in response to TNF-alpha is mediated, in part, by JNK and IKK
Yamaguchi et al., Hypertens Res 2003 (Arteriosclerosis...) : TNF-alpha significantly ( p < 0.05 ) inhibited IRS-1 phosphorylation by insulin but had no effect on ERK in L6 ... TNF-alpha had no effect on either IRS-1 phosphorylation or ERK in VSMC
Kirwan et al., Biochem Soc Trans 2003 (Insulin Resistance) : Recent studies have shown that TNF-alpha can increase IRS-1 serine/threonine phosphorylation, which impairs IRS-1 docking to the insulin receptor, and this inhibits insulin signalling
Shi et al., J Biol Chem 2004 : The ameliorated insulin signaling in SOCS3-deficient adipocytes is mainly due to the suppression of tumor necrosis factor-alpha induced IRS1 and IRS2 protein degradation
Csehi et al., Biochem Biophys Res Commun 2005 : Here, we identify the death domain of TNF-R55 as responsible for the inhibitory effects of TNF on tyrosine phosphorylation of IRS-1 , implicating ceramide generated by A-SMase as a downstream mediator of inhibition of IR signaling
Kim et al., J Biol Chem 2005 (Inflammation) : In addition, using a phospho-specific antibody against IRS-1 phosphorylated at Ser ( 24 ), we found that interleukin-1 or TNF-alpha treatment of Fao cells stimulated increased phosphorylation of endogenous IRS-1 at Ser ( 24 )
Kanda et al., FASEB J 2006 (Hypertension...) : Furthermore, both fasudil and Y-27632 prevented the serine phosphorylation of IRS-1 induced by insulin and/or tumor necrosis factor-alpha in skeletal muscle cells
Imoto et al., Diabetes 2006 (Carcinoma, Hepatocellular...) : TNF-alpha significantly activated ASK1, increased serine phosphorylation of insulin receptor substrate (IRS)-1 , and decreased insulin stimulated tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt, and all of these effects were inhibited by overexpression of either UCP-1 or MnSOD
Nakamori et al., J Cell Biol 2006 : Myosin motor Myo1c and its receptor NEMO/IKK-gamma promote TNF-alpha induced serine307 phosphorylation of IRS-1 ... Increased Myo1c expression enhanced the NEMO-IRS-1 interaction, which is essential for TNF-alpha- induced phosphorylation of Ser307-IRS-1 ... NEMO expression also enhanced TNF-alpha induced Ser307-IRS-1 phosphorylation and inhibited glucose uptake
Strle et al., Endocrinology 2006 (Inflammation) : Consistent with these results, TNFalpha induces JNK binding to insulin receptor substrate 1 (IRS-1) but is unable to inhibit IGF-I induced IRS-1 tyrosine phosphorylation in myoblasts that are treated with the JNK peptide inhibitor
Svegliati-Baroni et al., Am J Pathol 2006 (Disease Models, Animal...) : HFD also decreased adiponectin mRNA and peroxisome proliferator activated receptor ( PPAR)-alpha expression in the visceral adipose tissue and the liver, respectively, and induced hepatic insulin resistance through TNF-alpha mediated c-Jun N-terminal kinase (JNK) dependent insulin receptor substrate-1Ser307 phosphorylation
Bouzakri et al., J Biol Chem 2007 (Insulin Resistance) : We tested whether mitogenic activated protein kinase kinase kinase kinase isoform 4 ( MAP4K4 ) causes the TNF-alpha induced negative regulation of extracellular signal regulated kinase-1/2 ( ERK-1/2 ), c-Jun NH2-terminal kinase (JNK), and the insulin receptor substrate-1 (IRS-1) on the insulin signaling pathway governing glucose metabolism
Moloney et al., Diabetes 2007 (Diabetes Mellitus...) : To define whether these observations were direct effects of the nutrient intervention, complimentary cell culture studies showed that c9,t11-CLA inhibited tumor necrosis factor-alpha induced downregulation of insulin receptor substrate 1 and GLUT4 mRNA expression and promoted insulin stimulated glucose transport in 3T3-L1 adipocytes compared with linoleic acid
Ishizuka et al., Endocrinology 2007 (Insulin Resistance) : TNFalpha transiently stimulated serine phosphorylation of IRS-1 from 10 min to 1 h, whereas insulin stimulated IRS-1 tyrosine phosphorylation was inhibited only after TNFalpha treatment longer than 4 h ... Interestingly, when IRS-1 serine phosphorylation was enhanced by TNFalpha or anisomycin in the presence of low-level SOCS3, IRS-1 degradation was remarkably enhanced
Li et al., Endocrinology 2007 : TNF-alpha increased p38 MAPK phosphorylation, potently stimulated IRS-1 serine phosphorylation, and blunted insulin stimulated IRS-1 tyrosine and Akt phosphorylation and eNOS activity
Nishikawa et al., Diabetes Res Clin Pract 2007 (Hyperglycemia...) : Here we demonstrate that TNF-alpha increases mitochondrial ROS production and ASK1 activity, and that these TNF-alpha induced phenomena associate with JNK activation, increase in Ser ( 307 ) phosphorylation of IRS-1 and decrease in insulin stimulated tyrosine phosphorylation of IRS-1, all of which are believed to be the molecular basis of TNF-alpha induced insulin resistance
Wang et al., J Neurosci Res 2007 : Because TNFalpha triggers phosphorylation of insulin receptor substrate 1 (IRS-1) on serine residues ( pS-IRS-1 ; Rui et al. [ 2001 ] J. Clin
Austin et al., Diabetes 2008 (Insulin Resistance) : Conversely, TNF-alpha induced increases in insulin receptor substrate-1 serine phosphorylation ( Ser ( 312 ) ), Jun NH ( 2 ) -terminal kinase phosphorylation, and extracellular signal related kinase-1/2 mitogen activated protein kinase ( MAPK ) phosphorylation were unaltered by siRNA mediated IKKbeta reduction
Zhang et al., J Biol Chem 2008 (Insulin Resistance) : RNAi knockdown demonstrated an important role for S6K1 in mediating TNF-alpha induced IRS-1 inhibition that led to impaired insulin stimulated glucose uptake in adipocytes ... Expression of a dominant negative S6K1 mutant prevented TNF induced Ser-270 phosphorylation and IRS-1 protein degradation
Nishiumi et al., Toxicological sciences : an official journal of the Society of Toxicology 2010 (Insulin Resistance) : Anti-TNF-alpha neutralization antibody and silencing of TNF-alpha receptor 1 (TNFR1) diminished the TCDD induced downregulation of IRbeta, IRS1 , and GLUT4 ... Taken together, TCDD stimulates expression and secretion of TNF-alpha in adipocytes through activation of AhR, ERK1/2, and JNK, and the secreted TNF-alpha causes the downregulation of IRbeta, IRS1 , and GLUT4 through TNFR1, resulting in insulin resistance
Moon et al., Exp Mol Med 2010 (Diabetes Mellitus, Experimental...) : The TNFalpha induced suppression of the tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1) and Akt in 3T3-L1 adipocytes was also reversed by SAM
Natalicchio et al., Endocrinology 2010 : When cells were pretreated with exendin-4, TNFalpha induced JNK and IRS-1/2 serine phosphorylation was markedly reduced, Akt phosphorylation was increased, caspase-3 and Bcl-2 protein levels were restored to normal, and TNFalpha induced apoptosis was inhibited by 50 %
Hemi et al., Diabetes 2011 (Insulin Resistance) : When cells were incubated with specific ErbB receptors antagonists or in cells lacking ErbB receptors, anisomycin- and TNF induced IRS-1 serine phosphorylation was attenuated, despite intact p38MAPK activation
Jia et al., Mol Cell Biochem 2013 (Alzheimer Disease...) : TNF-a/c-Jun N-terminal kinase (JNK) signaling plays a central role in serine phosphorylation of insulin receptor substrate-1 (IRS-1)
Shibata et al., J Pharmacol Sci 2013 (Diabetes Mellitus, Type 2...) : Inhibition of the TNF-a Induced Serine Phosphorylation of IRS-1 at 636/639 by AICAR ... Here we investigated the role of AMPK in serine phosphorylation of IRS-1 at 636/639 and 307, which is induced by tumor necrosis factor (TNF)-a in 3T3L1 adipocytes ... We demonstrated that the AMPK activator 5-aminoimidazole-4-carboxamide-1-d-ribofuranoside ( AICAR ) significantly inhibited the TNF-a induced serine phosphorylation of IRS-1 at 636/639 and 307 by suppression of extracellular signal regulated kinase ( ERK ) phosphorylation but not c-Jun-NH2-terminal kinase (JNK) phosphorylation ... In conclusion, we propose a new mechanism in which AICAR suppresses TNF-a induced serine phosphorylation of IRS-1 at 636/639 and 307 by enhancing the interaction between ERK and DUSP9/MKP-4
Kanety et al., J Biol Chem 1995 (Insulin Resistance) : Tumor necrosis factor alpha induced phosphorylation of insulin receptor substrate-1 (IRS-1) ... TNF effect on IRS-1 in Fao hepatoma cells was not associated with a significant reduction in insulin receptor tyrosine kinase activity as measured in vitro but impaired the association of IRS-1 with phosphatidylinositol 3-kinase, localizing TNF impact to IRS-1 ... TNF did not increase protein-tyrosine phosphatase activity and protein-tyrosine phosphatase inhibition by vanadate did not change TNF effect on IRS-1 tyrosine phosphorylation, suggesting that protein-tyrosine phosphatases are not involved in this TNF effect ... In contrast, TNF increased IRS-1 phosphorylation on serine residues, leading to a decrease in its electrophoretic mobility ... TNF effect on IRS-1 tyrosine phosphorylation was not abolished by inhibiting protein kinase C using staurosporine, while inactivation of Ser/Thr phosphatases by calyculin A and okadaic acid mimicked it ... Our data suggest that TNF induces serine phosphorylation of IRS-1 through inhibition of serine phosphatases or activation of serine kinases other than protein kinase C
Guo et al., J Biol Chem 1996 : Tumor necrosis factor promotes phosphorylation and binding of insulin receptor substrate 1 to phosphatidylinositol 3-kinase in 3T3-L1 adipocytes ... In murine 3T3-L1 adipocytes, IRS-1 and PI 3-kinase phosphorylation and the association of these proteins are promoted by murine TNF , which interacts with the type 1 and type 2 TNF receptors ... Human TNF , which binds to the murine type 1 TNF receptor selectively, also promotes IRS-1 phosphorylation and binding of IRS-1 to PI 3-kinase
Ahmad et al., J Cell Biochem 1997 (Carcinoma, Hepatocellular) : In order to determine whether the effects of TNF-alpha might involve alterations in the expression of specific protein-tyrosine phosphatases ( PTPases ) that have been implicated in the regulation of growth factor receptor signalling, KRC-7 rat hepatoma cells were treated with TNF-alpha, and changes in overall tissue PTPase activity and the abundance of three major hepatic PTPases ( LAR, PTP1B, and SH-PTP2 ) were measured in addition to effects of TNF-alpha on ligand stimulated autophosphorylation of insulin and epidermal growth factor (EGF) receptors and insulin stimulated insulin receptor substrate-1 (IRS-1) phosphorylation ... TNF-alpha caused a dose dependent decrease in insulin stimulated IRS-1 phosphorylation and EGF stimulated receptor autophosphorylation to 47-50 % of control