PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 11438661-1 2001 A pathway sensitive to rapamycin, a selective inhibitor of mammalian target of rapamycin (mTOR), down-regulates effects of insulin such as activation of Akt (protein kinase B) via proteasomal degradation of insulin receptor substrate 1 (IRS-1). Sirolimus 23-32 insulin receptor substrate 1 Homo sapiens 207-235 12051762-5 2002 Rapamycin prevented the reduction of IRS-1 protein levels and insulin-induced PKB Ser-473 phosphorylation with a partial normalization of insulin-induced glucose transport. Sirolimus 0-9 insulin receptor substrate 1 Homo sapiens 37-42 11948686-2 2002 Inhibition of mTOR with rapamycin resulted in approximately 50% inhibition of the insulin-induced degradation of IRS-1. Sirolimus 24-33 insulin receptor substrate 1 Homo sapiens 113-118 15988698-7 2005 Rapamycin, an inhibitor or mTOR, could partially improve insulin-stimulated glucose uptake through maintaining IRS-1 protein levels. Sirolimus 0-9 insulin receptor substrate 1 Homo sapiens 111-116 15576463-8 2005 As in murine cells, rapamycin treatment of human adipocytes inhibited S6K1, blunted Ser636/639 phosphorylation of IRS-1, leading to increased Akt activation and glucose uptake by insulin. Sirolimus 20-29 insulin receptor substrate 1 Homo sapiens 114-119 15576463-9 2005 Further studies in 3T3-L1 adipocytes revealed that rapamycin prevented the relocalization of IRS-1 from the low-density membranes to the cytosol in response to insulin. Sirolimus 51-60 insulin receptor substrate 1 Homo sapiens 93-98 11438661-1 2001 A pathway sensitive to rapamycin, a selective inhibitor of mammalian target of rapamycin (mTOR), down-regulates effects of insulin such as activation of Akt (protein kinase B) via proteasomal degradation of insulin receptor substrate 1 (IRS-1). Sirolimus 23-32 insulin receptor substrate 1 Homo sapiens 237-242 11438661-3 2001 After prolonged insulin stimulation, inhibition of the redistribution of IRS-1 by rapamycin resulted in increased levels of IRS-1 and the associated phosphatidylinositol (PI) 3-kinase in both the LDM and cytosol, whereas the proteasome inhibitor lactacystin increased the levels only in the cytosol. Sirolimus 82-91 insulin receptor substrate 1 Homo sapiens 73-78 11438661-3 2001 After prolonged insulin stimulation, inhibition of the redistribution of IRS-1 by rapamycin resulted in increased levels of IRS-1 and the associated phosphatidylinositol (PI) 3-kinase in both the LDM and cytosol, whereas the proteasome inhibitor lactacystin increased the levels only in the cytosol. Sirolimus 82-91 insulin receptor substrate 1 Homo sapiens 124-129 10847581-5 2000 Adenovirus-mediated expression of a membrane-targeted form of the p110 subunit of phosphatidylinositol (PI) 3-kinase (p110CAAX) induced a mobility shift and degradation of IRS-1, both of which were inhibited by rapamycin. Sirolimus 211-220 insulin receptor substrate 1 Homo sapiens 172-177 11287630-8 2001 mTOR induced the serine phosphorylation of IRS-1 (Ser-636/639), and such phosphorylation was inhibited by rapamycin. Sirolimus 106-115 insulin receptor substrate 1 Homo sapiens 43-48 11147790-6 2001 Incubation with okadaic acid increased the serine/threonine phosphorylation of IRS-1 and its degradation, mimicking insulin, and its effect was prevented by the proteasome inhibitor lactacystin, as well as by rapamycin. Sirolimus 209-218 insulin receptor substrate 1 Homo sapiens 79-84 11147790-4 2001 Wortmannin and rapamycin blocked this mobility shift of IRS-1, maintained the insulin-induced tyrosine phosphorylation of IRS-1, and blocked its degradation. Sirolimus 15-24 insulin receptor substrate 1 Homo sapiens 56-61 11147790-4 2001 Wortmannin and rapamycin blocked this mobility shift of IRS-1, maintained the insulin-induced tyrosine phosphorylation of IRS-1, and blocked its degradation. Sirolimus 15-24 insulin receptor substrate 1 Homo sapiens 122-127 28831455-2 2017 One potential and current model that explains Akt activation induced by the mTOR inhibitor rapamycin is the relief of mTORC1/p70S6K-mediated feedback inhibition of IRS-1/PI3K/Akt signaling, although this has not been experimentally proven. Sirolimus 91-100 insulin receptor substrate 1 Homo sapiens 164-169 31005665-0 2019 Nicotine inhibits rapamycin-induced pain through activating mTORC1/S6K/IRS-1-related feedback inhibition loop. Sirolimus 18-27 insulin receptor substrate 1 Homo sapiens 71-76 33422633-8 2021 Interestingly, inhibition of mTORC1-S6K1 pathway using rapamycin significantly restored the IRS-1/Akt/eNOS activation, suggesting a feedback regulation of IRS-1/Akt signal through S6K1. Sirolimus 55-64 insulin receptor substrate 1 Homo sapiens 92-97 33422633-8 2021 Interestingly, inhibition of mTORC1-S6K1 pathway using rapamycin significantly restored the IRS-1/Akt/eNOS activation, suggesting a feedback regulation of IRS-1/Akt signal through S6K1. Sirolimus 55-64 insulin receptor substrate 1 Homo sapiens 155-160 29483302-7 2018 In tumor cells engineered to express NLS-IRS-1, the IRS-1/LC3 nuclear structures repress autophagy induced by either amino acid starvation or rapamycin treatment. Sirolimus 142-151 insulin receptor substrate 1 Homo sapiens 41-46 29483302-7 2018 In tumor cells engineered to express NLS-IRS-1, the IRS-1/LC3 nuclear structures repress autophagy induced by either amino acid starvation or rapamycin treatment. Sirolimus 142-151 insulin receptor substrate 1 Homo sapiens 52-57 27686967-5 2016 Treatment of brown adipocytes with rapamycin for 16h significantly decreased insulin receptor substrate 1 (IRS1) protein expression and insulin-mediated protein kinase B (Akt) phosphorylation. Sirolimus 35-44 insulin receptor substrate 1 Homo sapiens 77-105 27686967-5 2016 Treatment of brown adipocytes with rapamycin for 16h significantly decreased insulin receptor substrate 1 (IRS1) protein expression and insulin-mediated protein kinase B (Akt) phosphorylation. Sirolimus 35-44 insulin receptor substrate 1 Homo sapiens 107-111 25813876-6 2015 The mTOR complex (C)1/S6K1 blocker rapamycin inhibited the phosphorylation of IRS-1 at Ser636 in cells overexpressing alpha-Syn, suggesting that mTORC1/S6K1 activation by alpha-Syn causes feedback inhibition of insulin signaling via suppression of IRS-1 function. Sirolimus 35-44 insulin receptor substrate 1 Homo sapiens 78-83 25813876-6 2015 The mTOR complex (C)1/S6K1 blocker rapamycin inhibited the phosphorylation of IRS-1 at Ser636 in cells overexpressing alpha-Syn, suggesting that mTORC1/S6K1 activation by alpha-Syn causes feedback inhibition of insulin signaling via suppression of IRS-1 function. Sirolimus 35-44 insulin receptor substrate 1 Homo sapiens 248-253 24936056-5 2014 Notably, depletion/inhibition of PRCP/PREP destabilized IRS-1 in the cells treated with rapamycin, blocking the feedback activation PI3K/AKT. Sirolimus 88-97 insulin receptor substrate 1 Homo sapiens 56-61 25875045-8 2015 Consistent with this notion, Ucn 2 reduced insulin-induced tyrosine phosphorylation of IRS-1, and treatment with rapamycin reversed the inhibitory effect of Ucn 2 on IRS-1 and Akt phosphorylation. Sirolimus 113-122 insulin receptor substrate 1 Homo sapiens 166-171 21701901-11 2012 Sirolimus, a specific inhibitor of mTOR pathway, inhibited MHV68-induced hepatic expression of serine p-IRS-1, increased total IRS-1 levels and improved MHV68-induced hepatic insulin resistance. Sirolimus 0-9 insulin receptor substrate 1 Homo sapiens 104-109 22890326-4 2013 Rapamycin increases epidermal Akt1 phosphorylation via inhibition of the mTOR complex 1-dependent regulation of insulin receptor substrate-1. Sirolimus 0-9 insulin receptor substrate 1 Homo sapiens 112-140 21701901-11 2012 Sirolimus, a specific inhibitor of mTOR pathway, inhibited MHV68-induced hepatic expression of serine p-IRS-1, increased total IRS-1 levels and improved MHV68-induced hepatic insulin resistance. Sirolimus 0-9 insulin receptor substrate 1 Homo sapiens 127-132 22028412-6 2012 An inhibitor of mTOR, rapamycin, attenuated the ANG II-stimulated phosphorylation of p70S6K and phosphorylation of IRS-1 (Ser(636/639)) and blocked the ability of ANG II to impair insulin-stimulated phosphorylation of eNOS, nitric oxide production, and mesenteric-arteriole vasodilation. Sirolimus 22-31 insulin receptor substrate 1 Homo sapiens 115-120 22281494-3 2012 However, the inhibition of mTOR activity by rapamycin (inhibitor of several intracellular pathways including S6K1 pathways) reversed the ER stress-reduced tyrosine phosphorylation of IRS-1 and glucose uptake. Sirolimus 44-53 insulin receptor substrate 1 Homo sapiens 183-188 21478152-8 2011 Resistin also stimulated the activation of p70(S6K), a downstream kinase target of mTOR, and increased phosphorylation of the IRS1 serine 636/639 residues, whereas treatment with rapamycin reduced the phosphorylation of these residues. Sirolimus 179-188 insulin receptor substrate 1 Homo sapiens 126-130 21602475-11 2011 Mimicking AMPK activators in the presence of insulin, rapamycin inhibited p70S6K and reduced IRS-1 phosphorylation on serine, resulting in the overphosphorylation of PKB/Akt and AS160. Sirolimus 54-63 insulin receptor substrate 1 Homo sapiens 93-98 20936651-5 2011 IRS-1 (Ser302) phosphorylation was abolished by wortmannin and rapamycin, suggesting a feedback from the PI3K pathway on insulin signalling. Sirolimus 63-72 insulin receptor substrate 1 Homo sapiens 0-5 20135346-3 2010 As mTOR inhibition by rapamycin is associated with attenuation of negative feedback to IRS-1, rapamycin is known to increase activation of AKT, which may reduce its anti-neoplastic activity. Sirolimus 22-31 insulin receptor substrate 1 Homo sapiens 87-92 19356713-5 2009 Insulin resistance induced by HF/BCAA feeding was accompanied by chronic phosphorylation of mTOR, JNK, and IRS1Ser307 and by accumulation of multiple acylcarnitines in muscle, and it was reversed by the mTOR inhibitor, rapamycin. Sirolimus 219-228 insulin receptor substrate 1 Homo sapiens 107-111 19887566-7 2010 Insulin phosphorylation of S6K1 correlated with IRS-1 ser1101 phosphorylation and the mTOR-S6K1 pathway inhibitor rapamycin prevented IRS-1 serine phosphorylation. Sirolimus 114-123 insulin receptor substrate 1 Homo sapiens 134-139 19887566-8 2010 The proteasomal inhibitor epoxomicin and the lysosomal pathway inhibitor 3-methyladenine prevented the degradation of IRS-1 and IR by insulin, respectively, and pretreatment with rapamycin, epoxomicin, or 3-methyladenine prevented attenuation of insulin signaling by long-term insulin exposure. Sirolimus 179-188 insulin receptor substrate 1 Homo sapiens 118-123 17334390-1 2007 Rapamycin, a natural product inhibitor of the Raptor-mammalian target of rapamycin complex (mTORC1), is known to induce Protein kinase B (Akt/PKB) Ser-473 phosphorylation in a subset of human cancer cell lines through inactivation of S6K1, stabilization of insulin receptor substrate (IRS)-1, and increased signaling through the insulin/insulin-like growth factor-I/phosphatidylinositol 3-kinase (PI3K) axis. Sirolimus 0-9 insulin receptor substrate 1 Homo sapiens 257-291 18922904-8 2008 Mechanistically, we find that inhibition of the MAPK pathway circumvents a negative feedback loop imposed on the IGF-IR- insulin receptor substrate 1 (IRS-1) signaling complex, a molecular scenario that parallels the negative feedback loop between mTOR-p70S6K and IRS-1 that mediates rapamycin-directed IGF-IR signaling. Sirolimus 284-293 insulin receptor substrate 1 Homo sapiens 151-156 17908691-0 2007 Rapamycin promotes vascular smooth muscle cell differentiation through insulin receptor substrate-1/phosphatidylinositol 3-kinase/Akt2 feedback signaling. Sirolimus 0-9 insulin receptor substrate 1 Homo sapiens 71-99 17908691-4 2007 Here, we show that rapamycin activates Akt and induces contractile protein expression in human VSMC in an insulin-like growth factor I-dependent manner, by relieving S6K1-dependent negative regulation of insulin receptor substrate-1 (IRS-1). Sirolimus 19-28 insulin receptor substrate 1 Homo sapiens 204-232 17908691-4 2007 Here, we show that rapamycin activates Akt and induces contractile protein expression in human VSMC in an insulin-like growth factor I-dependent manner, by relieving S6K1-dependent negative regulation of insulin receptor substrate-1 (IRS-1). Sirolimus 19-28 insulin receptor substrate 1 Homo sapiens 234-239 17908691-7 2007 Rapamycin inhibits S6K1-dependent IRS-1 serine phosphorylation, increases IRS-1 protein levels, and promotes association of tyrosine-phosphorylated IRS-1 with PI3K. Sirolimus 0-9 insulin receptor substrate 1 Homo sapiens 34-39 17908691-7 2007 Rapamycin inhibits S6K1-dependent IRS-1 serine phosphorylation, increases IRS-1 protein levels, and promotes association of tyrosine-phosphorylated IRS-1 with PI3K. Sirolimus 0-9 insulin receptor substrate 1 Homo sapiens 74-79 17908691-7 2007 Rapamycin inhibits S6K1-dependent IRS-1 serine phosphorylation, increases IRS-1 protein levels, and promotes association of tyrosine-phosphorylated IRS-1 with PI3K. Sirolimus 0-9 insulin receptor substrate 1 Homo sapiens 74-79 18264722-0 2008 Antineoplastic effect of rapamycin is potentiated by inhibition of IRS-1 signaling in prostate cancer cells xenografts. Sirolimus 25-34 insulin receptor substrate 1 Homo sapiens 67-72 16452206-4 2006 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. Sirolimus 224-233 insulin receptor substrate 1 Homo sapiens 41-69 16227402-9 2005 Furthermore, rapamycin prevented serine phosphorylation of IRS-1, enhanced IRS-1 association with IGF-I receptors, and prevented IRS-1 degradation. Sirolimus 13-22 insulin receptor substrate 1 Homo sapiens 59-64 16227402-9 2005 Furthermore, rapamycin prevented serine phosphorylation of IRS-1, enhanced IRS-1 association with IGF-I receptors, and prevented IRS-1 degradation. Sirolimus 13-22 insulin receptor substrate 1 Homo sapiens 75-80 16227402-9 2005 Furthermore, rapamycin prevented serine phosphorylation of IRS-1, enhanced IRS-1 association with IGF-I receptors, and prevented IRS-1 degradation. Sirolimus 13-22 insulin receptor substrate 1 Homo sapiens 75-80 16099428-1 2005 In 3T3-L1 adipocytes, insulin or anisomycin stimulated phosphorylation of IRS-1 at Ser(307) and Ser(636/639), both of which were partially reduced by the mTOR inhibitor, rapamycin, or the JNK inhibitor, SP600125, and were further inhibited by a combination of them. Sirolimus 170-179 insulin receptor substrate 1 Homo sapiens 74-79 17329620-11 2007 Rapamycin partially inhibited this increase in mTOR-mediated S6K phosphorylation and IRS-1 Ser312 and Ser636 phosphorylation. Sirolimus 0-9 insulin receptor substrate 1 Homo sapiens 85-90 16129690-4 2005 Inhibition of serine 307 phosphorylation by rapamycin mimicked type 2 diabetes and reduced the sensitivity of IRS1 tyrosine phosphorylation in response to insulin, while stimulation of the phosphorylation by okadaic acid, in cells from patients with type 2 diabetes, rescued cells from insulin resistance. Sirolimus 44-53 insulin receptor substrate 1 Homo sapiens 110-114