PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 34775001-2 2022 There is a growing body of evidence from both pre-clinical studies and human cohorts indicating that reactive oxygen species, such as the superoxide radical anion and hydrogen peroxide are key players in the development of insulin resistance. Superoxides 138-162 insulin Homo sapiens 223-230 27064285-5 2016 In human grafts, chronic insulin resistance decreased antioxidant enzyme expression and increased superoxide and amyloid formation. Superoxides 98-108 insulin Homo sapiens 25-32 32171979-7 2020 The NSAPP pathway is an oxide transport chain that begins when insulin stimulates NADPH oxidase-4 to generate superoxide (O2 -). Superoxides 110-120 insulin Homo sapiens 63-70 31634466-2 2020 Based on data obtained at the whole cell level using poorly specific chemical probes, reactive oxygen species (ROS) such as superoxide and hydrogen peroxide have been proposed to contribute to the stimulation of insulin secretion by nutrients (positive role) and to the alterations of cell survival and secretory function in T2D (negative role). Superoxides 124-134 insulin Homo sapiens 212-219 28891325-4 2018 Low-grade inflammation, oxidative stress, balance between superoxide and nitric oxide, and the infiltration of macrophages, T cells, and B cells in insulin-sensitive tissues lead to metabolic impairment and accelerated aging. Superoxides 58-68 insulin Homo sapiens 148-155 29402381-5 2018 Specifically, lowering of mitochondrial CoQ caused insulin resistance in adipocytes as a result of increased superoxide/hydrogen peroxide production via complex II. Superoxides 109-119 insulin Homo sapiens 51-58 28600985-7 2017 In HAMECs, insulin-induced time-dependent increases in Nox2 expression and P47phox phosphorylation were echoed by elevations of superoxide production. Superoxides 128-138 insulin Homo sapiens 11-18 35164215-6 2022 ROS such as hydrogen peroxide and the superoxide anion introduce chemical changes virtually in all cellular components, causing deleterious effects on the islets of beta-cells, in turn affecting insulin production. Superoxides 38-54 insulin Homo sapiens 195-202 30935113-8 2019 Unexpectedly, however, elevated ACSL-5 expression increased mitochondrial superoxide production (+30%), which was associated with a significant reduction (p < 0.05) in insulin-stimulated p-Akt and p-AS160 protein levels. Superoxides 74-84 insulin Homo sapiens 171-178 30317185-2 2018 NOX-generated superoxide has been suggested to promote insulin resistance in the liver. Superoxides 14-24 insulin Homo sapiens 55-62 28600985-11 2017 Finally, insulin induced nitrotyrosine formation which was reversed by inhibiting NO or superoxide generation. Superoxides 88-98 insulin Homo sapiens 9-16 27920123-6 2017 Insulin-stimulated phosphorylation of protein kinase B was increased in hIRECO EC as was Nox2 NADPH oxidase-dependent generation of superoxide, whereas insulin-stimulated and shear stress-stimulated eNOS activations were blunted. Superoxides 132-142 insulin Homo sapiens 0-7 27920123-9 2017 CONCLUSIONS: Enhancing insulin sensitivity specifically in EC leads to a paradoxical decline in endothelial function, mediated by increased tyrosine phosphorylation of eNOS and excess Nox2-derived superoxide. Superoxides 197-207 insulin Homo sapiens 23-30 27920123-10 2017 Increased EC insulin sensitivity leads to a proatherosclerotic imbalance between NO and superoxide. Superoxides 88-98 insulin Homo sapiens 13-20 27920123-12 2017 This study demonstrates for the first time that increased endothelial insulin sensitivity leads to a proatherosclerotic imbalance between NO and superoxide. Superoxides 145-155 insulin Homo sapiens 70-77 25460870-1 2015 BACKGROUND: Hyperglycemia in patients with acute coronary syndromes is associated with poor outcomes, and its rapid correction with insulin infusion has been shown to restore platelet responsiveness to nitric oxide and to suppress superoxide (O2(-)) generation. Superoxides 231-241 insulin Homo sapiens 132-139 25875935-9 2015 Insulin and apocynin attenuate ROS and O2 - generation, and restored vascular reactivity to U46619 and CGRP. Superoxides 39-41 insulin Homo sapiens 0-7 25460870-1 2015 BACKGROUND: Hyperglycemia in patients with acute coronary syndromes is associated with poor outcomes, and its rapid correction with insulin infusion has been shown to restore platelet responsiveness to nitric oxide and to suppress superoxide (O2(-)) generation. Superoxides 243-245 insulin Homo sapiens 132-139 23349484-3 2013 Using three complementary methods to measure superoxide, we demonstrated higher levels of superoxide in insulin-resistant endothelial cells, which could be pharmacologically inhibited both acutely and chronically, using the Nox inhibitor gp91ds-tat. Superoxides 45-55 insulin Homo sapiens 104-111 24561577-0 2014 Rapid reaction of superoxide with insulin-tyrosyl radicals to generate a hydroperoxide with subsequent glutathione addition. Superoxides 18-28 insulin Homo sapiens 34-41 24561577-2 2014 We used insulin as a model to study the kinetics, mechanisms, and products of the reactions of radiation-induced or enzyme-generated protein-tyrosyl radicals with superoxide to demonstrate the feasibility of these reactions under oxidative stress conditions. Superoxides 163-173 insulin Homo sapiens 8-15 24561577-4 2014 However, in the presence of superoxide, dimerization was largely outcompeted by the reaction of superoxide with insulin-tyrosyl radicals. Superoxides 28-38 insulin Homo sapiens 112-119 24561577-4 2014 However, in the presence of superoxide, dimerization was largely outcompeted by the reaction of superoxide with insulin-tyrosyl radicals. Superoxides 96-106 insulin Homo sapiens 112-119 24561577-6 2014 Mass-spectrometry-based product analyses revealed the addition of superoxide to the insulin-Tyr14 radical to form the hydroperoxide. Superoxides 66-76 insulin Homo sapiens 84-91 23349484-3 2013 Using three complementary methods to measure superoxide, we demonstrated higher levels of superoxide in insulin-resistant endothelial cells, which could be pharmacologically inhibited both acutely and chronically, using the Nox inhibitor gp91ds-tat. Superoxides 90-100 insulin Homo sapiens 104-111 23349484-5 2013 siRNA-mediated knockdown of Nox2, which was specifically elevated in insulin-resistant endothelial cells, significantly reduced superoxide levels. Superoxides 128-138 insulin Homo sapiens 69-76 19357530-10 2009 NADPH oxidase-dependent superoxide production was augmented (P < 0.05) in insulin-resistant patients with respect to insulin-sensitive patients. Superoxides 24-34 insulin Homo sapiens 77-84 21838680-2 2011 The increased oxidative stress in subjects with type 2 diabetes is a consequence of several abnormalities, including hyperglycemia, insulin resistance, hyperinsulinemia, and dyslipidemia, each of which contributes to mitochondrial superoxide overproduction in endothelial cells of large and small vessels as well as the myocardium. Superoxides 231-241 insulin Homo sapiens 132-139 19357530-10 2009 NADPH oxidase-dependent superoxide production was augmented (P < 0.05) in insulin-resistant patients with respect to insulin-sensitive patients. Superoxides 24-34 insulin Homo sapiens 120-127 19357530-11 2009 The interaction between insulin resistance and abnormally high NADPH oxidase-mediated superoxide production was associated with the highest matrix metalloproteinase-9 values. Superoxides 86-96 insulin Homo sapiens 24-31 19357530-12 2009 Increased NADPH oxidase-dependent superoxide production was significantly associated with higher NADPH oxidase p22phox expression in insulin-resistant than in insulin-sensitive patients. Superoxides 34-44 insulin Homo sapiens 133-140 19357530-12 2009 Increased NADPH oxidase-dependent superoxide production was significantly associated with higher NADPH oxidase p22phox expression in insulin-resistant than in insulin-sensitive patients. Superoxides 34-44 insulin Homo sapiens 159-166 16528409-2 2006 In this report, we show that increased oxidation of FFAs in aortic endothelial cells without added insulin causes increased production of superoxide by the mitochondrial electron transport chain. Superoxides 138-148 insulin Homo sapiens 99-106 18569016-4 2008 The results showed that chronic insulin treatment significantly increased the intracellular generation of superoxide anion, hydrogen peroxide and hydroxyl radical. Superoxides 106-122 insulin Homo sapiens 32-39 17239711-0 2007 The deleterious effects of hyperglycemia on platelet function in diabetic patients with acute coronary syndromes mediation by superoxide production, resolution with intensive insulin administration. Superoxides 126-136 insulin Homo sapiens 175-182 17239711-10 2007 Intravenous insulin infusion resulted in a greater reduction (p < 0.001) in BSL, differentially improved platelet responsiveness to SNP (p = 0.049), and decreased O2- (p < 0.001) and ADMA levels (p = 0.049). Superoxides 166-168 insulin Homo sapiens 12-19 19439231-1 2009 Insulin stimulates superoxide (O(2)(-)) production in monocytes and macrophages. Superoxides 19-29 insulin Homo sapiens 0-7 19439231-1 2009 Insulin stimulates superoxide (O(2)(-)) production in monocytes and macrophages. Superoxides 31-39 insulin Homo sapiens 0-7 19439231-2 2009 However, the mechanisms through which insulin induces O(2)(-) production are not completely understood. Superoxides 54-58 insulin Homo sapiens 38-45 19439231-3 2009 In this study, we (a) characterized the enzyme and the pathways involved in insulin-stimulated O(2)(-) production in human monocytes and murine macrophages, and (b) analyzed the consequences of insulin-stimulated O(2)(-) production on the cellular phenotype in these cells. Superoxides 95-102 insulin Homo sapiens 76-83 19439231-3 2009 In this study, we (a) characterized the enzyme and the pathways involved in insulin-stimulated O(2)(-) production in human monocytes and murine macrophages, and (b) analyzed the consequences of insulin-stimulated O(2)(-) production on the cellular phenotype in these cells. Superoxides 213-220 insulin Homo sapiens 76-83 19439231-3 2009 In this study, we (a) characterized the enzyme and the pathways involved in insulin-stimulated O(2)(-) production in human monocytes and murine macrophages, and (b) analyzed the consequences of insulin-stimulated O(2)(-) production on the cellular phenotype in these cells. Superoxides 213-220 insulin Homo sapiens 194-201 19439231-4 2009 We showed that insulin stimulated O(2)(-) production, and promoted p47(phox) translocation to the plasma membrane. Superoxides 34-41 insulin Homo sapiens 15-22 19439231-8 2009 Small-interfering RNA-specific gene silencing targeted specifically against Nox2 reduced the cognate protein expression, decreased insulin-induced O(2)(-) production, inhibited the turn on of NFkappaB, p38MAPK, and ERK 1/2, and reduced cell proliferation in macrophages. Superoxides 147-154 insulin Homo sapiens 131-138 17602959-3 2007 The insulin-induced effects were prevented by cotreatment with either a superoxide scavenger or a peroxynitrite scavenger. Superoxides 72-82 insulin Homo sapiens 4-11 15111505-3 2004 Insulin treatment significantly increased intracellular superoxide anion (O(2)(-)) production, an effect completely abolished by Tiron, a cell-permeable superoxide dismutase (SOD) mimetic and by polyethylene glycol (PEG)-SOD, but not by PEG catalase. Superoxides 56-72 insulin Homo sapiens 0-7 16336581-7 2005 A direct correlation (r=0.441, P<0.05) was found between plasma insulin levels and NADPH oxidase-mediated *O2- production in patients. Superoxides 110-112 insulin Homo sapiens 67-74 15163543-14 2004 Although without supportive data, superoxide production induced by arsenic exposure can theoretically impair insulin secretion by interaction with uncoupling protein 2 (UCP2), and oxidative stress can also cause amyloid formation in the pancreas, which could progressively destroy the insulin-secreting beta cells. Superoxides 34-44 insulin Homo sapiens 109-116 15111505-4 2004 Furthermore, insulin-induced O(2)(-) production was attenuated by the NAD(P)H inhibitor apocynin, but not by rotenone or oxypurinol. Superoxides 29-36 insulin Homo sapiens 13-20 15111505-5 2004 Inhibition of the phosphatidylinositol 3"-kinase (PI 3"-kinase) pathway with LY294002 blocked insulin-stimulated O(2)(-) production, suggesting a direct involvement of PI 3"-kinase in the activation of NAD(P)H oxidase. Superoxides 113-120 insulin Homo sapiens 94-101 15111505-7 2004 In conclusion, these findings provided direct evidence that elevated insulin levels generate O(2)(-) by an NAD(P)H-dependent mechanism that involves the activation of PI 3"-kinase and stimulates ERK-1- and ERK-2-dependent pathways. Superoxides 93-100 insulin Homo sapiens 69-76 11642716-8 2001 In conclusion, we assume that the insulin-induced increase in chemiluminescence of platelet-rich plasma was due to increased production of NO* and superoxide free radicals forming peroxynitrite. Superoxides 147-157 insulin Homo sapiens 34-41 14679173-3 2003 A new study demonstrates that hyperglycemia-induced mitochondrial superoxide production activates uncoupling protein 2, which decreases the ATP/ADP ratio and thus reduces the insulin-secretory response. Superoxides 66-76 insulin Homo sapiens 175-182 11545628-3 2001 Insulin inhibits TNF alpha and enhances TGF beta production, augments nitric oxide synthesis and blocks superoxide anion generation. Superoxides 104-120 insulin Homo sapiens 0-7 15032648-8 2004 Under insulin-resistant conditions where BH(4) levels are suboptimal, in addition to a reduced synthesis of NO, an accelerated inactivation of NO by O(2)(-) within the vascular wall was observed. Superoxides 149-153 insulin Homo sapiens 6-13 14679178-6 2003 This study demonstrates that endogenously produced mitochondrial superoxide activates UCP2-mediated proton leak, thus lowering ATP levels and impairing glucose-stimulated insulin secretion. Superoxides 65-75 insulin Homo sapiens 171-178 12524232-7 2003 Insulin reduced mouse peritoneal macrophage (MPM) lipid peroxides content and superoxide anion release by up to 44% and 62%, respectively (P<0.01). Superoxides 78-94 insulin Homo sapiens 0-7 12323112-0 2002 Insulin"s stimulation of endothelial superoxide generation may reflect up-regulation of isoprenyl transferase activity that promotes rac translocation. Superoxides 37-47 insulin Homo sapiens 0-7 11461170-1 2001 Insulin seems to have the ability to suppress the production of tumor necrosis factor-alpha and superoxide anion, enhance the synthesis of nitric oxide and inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) through stimulation of nitric oxide. Superoxides 96-112 insulin Homo sapiens 0-7 11377135-1 2001 I suggest that insulin suppresses the secretion and antagonizes the harmful effects of tumor necrosis factor-alpha, macrophage migration-inhibitory factor, and superoxide anion. Superoxides 160-176 insulin Homo sapiens 15-22 10944918-5 2000 It has been investigated that the metabolic disorders associated with obesity enhance the superoxide production in the arterial walls through the insulin resistance. Superoxides 90-100 insulin Homo sapiens 146-153