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Citations to this article

Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site
Xue Liang Du, … , Chengyu Sui, Michael Brownlee
Xue Liang Du, … , Chengyu Sui, Michael Brownlee
Published November 1, 2001
Citation Information: J Clin Invest. 2001;108(9):1341-1348. https://doi.org/10.1172/JCI11235.
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Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site

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Abstract

Endothelial nitric oxide synthase (eNOS) is activated by phosphorylation of serine 1177 by the protein kinase Akt/PKB. Since hyperglycemia-induced mitochondrial superoxide overproduction increases O-linked N-acetylglucosamine modification and decreases O-linked phosphorylation of the transcription factor Sp1, the effect of hyperglycemia and the hexosamine pathway on eNOS was evaluated. In bovine aortic endothelial cells, hyperglycemia inhibited eNOS activity 67%, and treatment with glucosamine had a similar effect. Hyperglycemia-associated inhibition of eNOS was accompanied by a twofold increase in O-linked N-acetylglucosamine modification of eNOS and a reciprocal decrease in O-linked serine phosphorylation at residue 1177. Both the inhibition of eNOS and the changes in its post-translational modifications were reversed by antisense inhibition of glutamine:fructose-6-phosphate amidotransferase, the rate-limiting enzyme of the hexosamine pathway, or by blocking mitochondrial superoxide overproduction with uncoupling protein-1 (UCP-1) or manganese superoxide dismutase (MnSOD). Immunoblot analysis of cells expressing myc-tagged wild-type human eNOS confirmed the reciprocal increase in O-linked N-acetylglucosamine and decrease in O-linked serine 1177 phosphorylation in response to hyperglycemia. In contrast, when myc-tagged human eNOS carried a mutation at the Akt phosphorylation site (Ser1177), O-linked N-acetylglucosamine modification was unchanged by hyperglycemia and phospho-eNOS was undetectable. Similar changes in eNOS activity and covalent modification were found in aortae from diabetic animals. Chronic impairment of eNOS activity by this mechanism may partly explain the accelerated atherosclerosis of diabetes.

Authors

Xue Liang Du, Diane Edelstein, Stefanie Dimmeler, Qida Ju, Chengyu Sui, Michael Brownlee

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Diabetes 2018
Vascular endothelium dysfunction: a conservative target in metabolic disorders
S Jamwal, S Sharma
Inflammation Research 2018
Vascular endothelial dysfunction, a major mediator in diabetic cardiomyopathy
M Knapp, X Tu, R Wu
Acta Pharmacologica Sinica 2018
Glomerular Endothelial Cell Stress and Cross-Talk With Podocytes in Early Diabetic Kidney Disease
IS Daehn
Frontiers in Medicine 2018
Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome
RM da Costa, JF da Silva, JV Alves, TB Dias, DM Rassi, LV Garcia, N de Souza Lobato, RC Tostes
Frontiers in physiology 2018
Mechanisms Underlying Chronic Binge Alcohol Exposure-Induced Uterine Artery Dysfunction in Pregnant Rat
VD Naik, K Davis-Anderson, K Subramanian, R Lunde-Young, MJ Nemec, J Ramadoss
Alcoholism, clinical and experimental research 2018
Differential Glycosylation and Modulation of Camel and Human HSP Isoforms in Response to Thermal and Hypoxic Stresses
A Hoter, M Amiri, A Prince, H Amer, M Warda, H Naim
International journal of molecular sciences 2018
Overexpression of steroid receptor coactivators alleviates hyperglycemia-induced endothelial cell injury in rats through activating the PI3K/Akt pathway
X Quan, C Liang, M Sun, L Zhang, X Li
Acta Pharmacologica Sinica 2018
DPP-4 inhibitors promote proliferation and migration of rat brain microvascular endothelial cells under hypoxic/high-glucose conditions, potentially through the SIRT1/HIF-1/VEGF pathway
DH Mi, HJ Fang, GH Zheng, XH Liang, YR Ding, X Liu, LP Liu
CNS Neuroscience & Therapeutics 2018
Clinical Implications of Serial Glucose Measurements in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis
JT Kim, SY Lee, DS Yoo, JS Lee, SH Kim, KH Choi, MS Park, KH Cho
Scientific Reports 2018
Endothelial Cell Metabolism
G Eelen, P de Zeeuw, L Treps, U Harjes, BW Wong, P Carmeliet
Physiological reviews 2018
The Vasculature in Prediabetes
DH Wasserman, TJ Wang, NJ Brown
Circulation research 2018
Mechanism of Development of Atherosclerosis and Cardiovascular Disease in Diabetes Mellitus
N Katakami
Journal of Atherosclerosis and Thrombosis 2018
Is there a Chance to Promote Arteriogenesis by DPP4 Inhibitors Even in Type 2 Diabetes? A Critical Review
S Vedantham, AK Kluever, E Deindl
Cells 2018
O-Linked β-N-acetylglucosamine (O-GlcNAc) modification: a new pathway to decode pathogenesis of diabetic retinopathy
Z Gurel, N Sheibani
Clinical Science 2018
A mini-network balance model for evaluating the progression of cardiovascular complications in Goto-Kakizaki rats
H Jiang, Y Wang, C Wei, X Zhang, H Liu, X Liu
Acta Pharmacologica Sinica 2017
Effect of pregabalin administration upon reperfusion in a rat model of hyperglycemic stroke: Mechanistic insights associated with high-mobility group box 1
Y Song, JH Jun, EJ Shin, YL Kwak, JS Shin, JK Shim, TV Arumugam
PloS one 2017
Oleanolic acid ameliorates high glucose-induced endothelial dysfunction via PPARδ activation
Z Zhang, M Jiang, X Xie, H Yang, X Wang, L Xiao, N Wang
Scientific Reports 2017
The Role of O-GlcNAcylation in Perivascular Adipose Tissue Dysfunction of Offspring of High-Fat Diet-Fed Rats
KE Zaborska, G Edwards, C Austin, M Wareing
Journal of Vascular Research 2017
The emerging link between O-GlcNAcylation and neurological disorders
X Ma, H Li, Y He, J Hao
Cellular and Molecular Life Sciences 2017
Real-time visualization of distinct nitric oxide generation of nitric oxide synthase isoforms in single cells
E Eroglu, S Hallström, H Bischof, M Opelt, K Schmidt, B Mayer, M Waldeck-Weiermair, WF Graier, R Malli
Nitric Oxide 2017
Altered Semmes–Weinstein monofilament test results are associated with oxidative stress markers in type 2 diabetic subjects
S Martinez-Hervás, MM Mendez, J Folgado, C Tormos, P Ascaso, M Peiró, JT Real, JF Ascaso
Journal of Translational Medicine 2017
Central Role of Metabolism in Endothelial Cell Function and Vascular Disease
L Bierhansl, LC Conradi, L Treps, M Dewerchin, P Carmeliet
Physiology (Bethesda, Md.) 2017
Macrovascular Complications in Patients with Diabetes and Prediabetes
D Huang, M Refaat, K Mohammedi, A Jayyousi, JA Suwaidi, CA Khalil
BioMed Research International 2017
Allopurinol protects human glomerular endothelial cells from high glucose-induced reactive oxygen species generation, p53 overexpression and endothelial dysfunction
T Eleftheriadis, G Pissas, G Antoniadi, V Liakopoulos, I Stefanidis
International Urology and Nephrology 2017
Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats
HF Hao, LM Liu, CS Pan, CS Wang, YS Gao, JY Fan, JY Han
Frontiers in physiology 2017
Cavin-1 regulates caveolae-mediated LDL transcytosis: crosstalk in an AMPK/eNOS/ NF-κB/Sp1 loop
XL Bai, XY Yang, JY Li, Y Li, X Jia, ZF Xiong, YM Wang, S Jin
Oncotarget 2017
The Role of Stress-Induced O-GlcNAc Protein Modification in the Regulation of Membrane Transport
V Fisi, A Miseta, T Nagy
Oxidative medicine and cellular longevity 2017
Tryptophan depletion under conditions that imitate insulin resistance enhances fatty acid oxidation and induces endothelial dysfunction through reactive oxygen species-dependent and independent pathways
T Eleftheriadis, G Pissas, M Sounidaki, G Antoniadi, C Rountas, V Liakopoulos, loannis Stefanidis
Molecular and Cellular Biochemistry 2017
Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle
RS Lee-Young, NJ Hoffman, KT Murphy, DC Henstridge, D Samocha-Bonet, AL Siebel, P Iliades, B Zivanovic, YH Hong, TD Colgan, MJ Kraakman, CR Bruce, P Gregorevic, GK McConell, GS Lynch, GR Drummond, BA Kingwell, JR Greenfield, MA Febbraio
Molecular Metabolism 2016
Molecular and Cellular Mechanisms of Cardiovascular Disorders in Diabetes
MS Shah, M Brownlee
Circulation research 2016
Activation of general control nonderepressible 2 kinase protects human glomerular endothelial cells from harmful high-glucose-induced molecular pathways
T Eleftheriadis, K Tsogka, G Pissas, G Antoniadi, V Liakopoulos, I Stefanidis
International Urology and Nephrology 2016
Glycemic Control in Coronary Revascularization
F Ujueta, EN Weiss, SP Sedlis, B Shah
Current Treatment Options in Cardiovascular Medicine 2016
Understanding the Causes and Implications of Endothelial Metabolic Variation in Cardiovascular Disease through Genome-Scale Metabolic Modeling
S McGarrity, H Halldórsson, S Palsson, PI Johansson, Ó Rolfsson
Frontiers in Cardiovascular Medicine 2016
Redox biology and the interface between bioenergetics, autophagy and circadian control of metabolism
AR Wende, ME Young, J Chatham, J Zhang, NS Rajasekaran, VM Darley-Usmar
Free radical biology & medicine 2016
Glucose and acute exercise influence factors secreted by circulating angiogenic cells in vitro
S Witkowski, G Guhanarayan, R Burgess
Physiological Reports 2016
(-)-Epicatechin-induced recovery of mitochondria from simulated diabetes: Potential role of endothelial nitric oxide synthase
I Ramirez-Sanchez, A Rodriguez, A Moreno-Ulloa, G Ceballos, F Villarreal
Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease 2016
Dynamin-related protein 1 mediates low glucose-induced endothelial dysfunction in human arterioles
MJ Tanner, J Wang, R Ying, TB Suboc, M Malik, A Couillard, A Branum, V Puppala, ME Widlansky
American journal of physiology. Heart and circulatory physiology 2016
Oxidative Stress Genes, Antioxidants and Coronary Artery Disease in Type 2 Diabetes Mellitus.
Tibaut M, Petrovič D
Cardiovascular & hematological agents in medicinal chemistry 2016
Mechanisms of distal axonal degeneration in peripheral neuropathies
CR Christopher, H Ahmet
Neuroscience Letters 2015
How do high glycemic load diets influence coronary heart disease?
MJ Mathews, L Liebenberg, EH Mathews
Nutrition & Metabolism 2015
The mechanism by which moderate alcohol consumption influences coronary heart disease
MJ Mathews, L Liebenberg, EH Mathews
Nutrition Journal 2015
Mechanisms and consequences of endothelial nitric oxide synthase dysfunction in hypertension:
Q Li, JY Youn, H Cai
Journal of Hypertension 2015
Hyperglycaemia Enhances Nitric Oxide Production in Diabetes: A Study from South Indian Patients
R Adela, SK Nethi, PK Bagul, AK Barui, S Mattapally, M Kuncha, CR Patra, PN Reddy, SK Banerjee, AV Gomes
PloS one 2015
Insights into the molecular mechanisms of diabetes-induced endothelial dysfunction: focus on oxidative stress and endothelial progenitor cells
MI Saad, TM Abdelkhalek, MM Saleh, MA Kamel, M Youssef, SH Tawfik, H Dominguez
Endocrine 2015
Recurrent hypoinsulinemic hyperglycemia in neonatal rats increases PARP-1 and NF-κB expression and leads to microglial activation in the cerebral cortex
T Gisslen, K Ennis, V Bhandari, R Rao
Pediatric Research 2015
High glucose induces and activates Toll-like receptor 4 in endothelial cells of diabetic retinopathy
L Wang, J Wang, J Fang, H Zhou, X Liu, SB Su
Diabetology & metabolic syndrome 2015
O -GlcNAcase overexpression reverses coronary endothelial cell dysfunction in type 1 diabetic mice
A Makino, A Dai, Y Han, KD Youssef, W Wang, R Donthamsetty, BT Scott, H Wang, WH Dillmann
American journal of physiology. Cell physiology 2015
MORPHOLOGICAL CONTROL OF MITOCHONDRIAL BIOENERGETICS
Yu T, Wang L, Yoon Y
2015
Renal Response to L-Arginine in Diabetic Rats. A Possible Link between Nitric Oxide System and Aquaporin-2
MC Ortiz, MF Borghese, SE Balonga, A Lavagna, AL Filipuzzi, R Elesgaray, MA Costa, MP Majowicz
PloS one 2014
O-GlcNAc and the cardiovascular system
S Dassanayaka, SP Jones
Pharmacology & Therapeutics 2014
Glycosylation of the Nuclear Pore: Glycosylation of the Nuclear Pore
B Li, JJ Kohler
Traffic (Copenhagen, Denmark) 2014
Automated quantification reveals hyperglycemia inhibits endothelial angiogenic function
AR Prisco, JD Bukowy, BR Hoffmann, JR Karcher, EC Exner, AS Greene
PloS one 2014
REGULATION OF OBESITY AND INSULIN RESISTANCE BY NITRIC OXIDE
BE Sansbury, BG Hill
Free radical biology & medicine 2014
PPARβ activation restores the high glucose-induced impairment of insulin signalling in endothelial cells: PPARβ and insulin signalling
AM Quintela, R Jiménez, L Piqueras, M Gómez-Guzmán, J Haro, MJ Zarzuelo, A Cogolludo, MJ Sanz, M Toral, M Romero, F Pérez-Vizcaíno, J Duarte
British Journal of Pharmacology 2014
Glucosamine-Induced OGT Activation Mediates Glucose Production Through Cleaved Notch1 and FoxO1, Which Coordinately Contributed to the Regulation of Maintenance of Self-Renewal in Mouse Embryonic Stem Cells
JH Jeon, HN Suh, MO Kim, JM Ryu, HJ Han
Stem Cells and Development 2014
Polyphenol fraction of extra virgin olive oil protects against endothelial dysfunction induced by high glucose and free fatty acids through modulation of nitric oxide and endothelin-1
CE Storniolo, J Roselló-Catafau, X Pintó, MT Mitjavila, JJ Moreno
Redox Biology 2014
Glycemic Variability and Acute Ischemic Stroke: The Missing Link?
EI González-Moreno, CR Cámara-Lemarroy, JG González-González, F Góngora-Rivera
Translational Stroke Research 2014
Cell biology of diabetic nephropathy: Roles of endothelial cells, tubulointerstitial cells and podocytes
Y Maezawa, M Takemoto, K Yokote
Journal of Diabetes Investigation 2014
Chemical tools to explore nutrient-driven O-GlcNAc cycling
EJ Kim, MR Bond, DC Love, JA Hanover
Critical Reviews in Biochemistry and Molecular Biology 2014
Oxidative Stress and Metabolic Pathologies: From an Adipocentric Point of View
SL Lay, G Simard, MC Martinez, R Andriantsitohaina
Oxidative Medicine & Cellular Longevity 2014
Endothelial dysfunction as a nexus for endothelial cell-cardiomyocyte miscommunication
TM Leucker, SP Jones
Frontiers in physiology 2014
Vitamins & Hormones
BE Sansbury, BG Hill
Vitamins & Hormones 2014
Glutathione depletion and acute exercise increase O-GlcNAc protein modification in rat skeletal muscle
TT Peternelj, SA Marsh, NA Strobel, A Matsumoto, D Briskey, VJ Dalbo, PS Tucker, JS Coombes
Molecular and Cellular Biochemistry 2014
Renoprotective, anti-oxidative and anti-apoptotic effects of oral low-dose quercetin in the C57BL/6J model of diabetic nephropathy
IB Gomes, ML Porto, MC Santos, BP Campagnaro, TM Pereira, SS Meyrelles, EC Vasquez
Lipids in Health and Disease 2014
Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease
J Goveia, P Stapor, P Carmeliet
EMBO Molecular Medicine 2014
Activation of AKT by O-Linked N-Acetylglucosamine Induces Vascular Calcification in Diabetes Mellitus
JM Heath, Y Sun, K Yuan, WE Bradley, S Litovsky, LJ Dell'Italia, JC Chatham, H Wu, Y Chen
Circulation research 2014
Protein O-GlcNAcylation and Cardiovascular (Patho)physiology
SA Marsh, HE Collins, JC Chatham
The Journal of biological chemistry 2014
High Glucose-induced O-GlcNAcylated Carbohydrate Response Element-binding Protein (ChREBP) Mediates Mesangial Cell Lipogenesis and Fibrosis: THE POSSIBLE ROLE IN THE DEVELOPMENT OF DIABETIC NEPHROPATHY
MJ Park, DI Kim, SK Lim, JH Choi, HJ Han, KC Yoon, SH Park
The Journal of biological chemistry 2014
Podocyte-Specific VEGF-A Gain of Function Induces Nodular Glomerulosclerosis in eNOS Null Mice
D Veron, PK Aggarwal, H Velazquez, M Kashgarian, G Moeckel, A Tufro
Journal of the American Society of Nephrology : JASN 2014
Regulation of eNOS enzyme activity by posttranslational modification.
Heiss EH, Dirsch VM
Current pharmaceutical design 2014
Vascular O-GlcNAcylation augments reactivity to constrictor stimuli by prolonging phosphorylated levels of the myosin light chain
Lima VV, Lobato NS, Filgueira FP, Webb RC, Tostes RC, Giachini FR
Brazilian Journal of Medical and Biological Research 2014
High glucose attenuates shear-induced changes in endothelial hydraulic conductivity by degrading the glycocalyx
SV Lopez-Quintero, LM Cancel, A Pierides, D Antonetti, DC Spray, JM Tarbell
PloS one 2013
Hepatic Extracellular Signal–Regulated Kinase 2 Suppresses Endoplasmic Reticulum Stress and Protects From Oxidative Stress and Endothelial Dysfunction
T Kujiraoka, Y Satoh, M Ayaori, Y Shiraishi, Y AraiNakaya, D Hakuno, H Yada, N Kuwada, S Endo, K Isoda, T Adachi
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease 2013
Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I
F Paneni, JA Beckman, MA Creager, F Cosentino
European Heart Journal 2013
Arginase inhibition mediates renal tissue protection in diabetic nephropathy by a nitric oxide synthase 3-dependent mechanism
H You, T Gao, TK Cooper, SM Morris, AS Awad
Kidney International 2013
The endothelial cell: an "early responder" in the development of insulin resistance
EJ Barrett, Z Liu
Reviews in endocrine & metabolic disorders 2013
Discovery and confirmation of O-GlcNAcylated proteins in rat liver mitochondria by combination of mass spectrometry and immunological methods
W Cao, J Cao, J Huang, J Yao, G Yan, H Xu, P Yang
PloS one 2013
Hyperglycemia induces differential change in oxidative stress at gene expression and functional levels in HUVEC and HMVEC
H Patel, J Chen, KC Das, M Kavdia
Cardiovascular Diabetology 2013
Protein O-GlcNAcylation in diabetes and diabetic complications
J Ma, GW Hart
Expert Review of Proteomics 2013
Akita spontaneously type 1 diabetic mice exhibit elevated vascular arginase and impaired vascular endothelial and nitrergic function
HA Toque, KP Nunes, L Yao, Z Xu, D Kondrikov, Y Su, RC Webb, RB Caldwell, RW Caldwell
PloS one 2013
Molecular biomarkers of vascular dysfunction in obstructive sleep apnea
E Kaczmarek, JP Bakker, DN Clarke, E Csizmadia, O Kocher, A Veves, F Tecilazich, CP O'Donnell, C Ferran, A Malhotra
PloS one 2013
Impairment of endothelial-myocardial interaction increases the susceptibility of cardiomyocytes to ischemia/reperfusion injury
TM Leucker, ZD Ge, J Procknow, Y Liu, Y Shi, M Bienengraeber, DC Warltier, JR Kersten
PloS one 2013
Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis
JA Groves, A Lee, G Yildirir, NE Zachara
Cell Stress and Chaperones 2013
Oxidative stress and myocardial injury in the diabetic heart
DM Ansley, B Wang
The Journal of Pathology 2013
Angiotensin II impairs endothelial nitric-oxide synthase bioavailability under free cholesterol-enriched conditions via intracellular free cholesterol-rich membrane microdomains
E Amiya, M Watanabe, N Takeda, T Saito, T Shiga, Y Hosoya, T Nakao, Y Imai, I Manabe, R Nagai, I Komuro, K Maemura
The Journal of biological chemistry 2013
Abnormal thiamine-dependent processes in Alzheimer's Disease. Lessons from diabetes
GE Gibson, JA Hirsch, RT Cirio, BD Jordan, P Fonzetti, J Elder
Molecular and Cellular Neuroscience 2013
Transforming Growth Factor-  Regulates Endothelial Function During High Salt Intake in Rats
WZ Ying, KJ Aaron, PW Sanders
Hypertension 2013
O-GlcNAc cycling: a link between metabolism and chronic disease.
Bond MR, Hanover JA
Annual Review of Nutrition 2013
Endothelial Dysfunction and Diabetes: Effects on Angiogenesis, Vascular Remodeling, and Wound Healing
GK Kolluru, SC Bir, CG Kevil
International Journal of Vascular Medicine 2012
Hyperglycemia and Endothelial Dysfunction in Atherosclerosis: Lessons from Type 1 Diabetes
SD Funk, A Yurdagul, AW Orr
International Journal of Vascular Medicine 2012
Bioenergetics in diabetic neuropathy: what we need to know
LM Hinder, AM Vincent, CF Burant, S Pennathur, EL Feldman
Journal of the Peripheral Nervous System 2012
The Role of Glucosamine-Induced ER Stress in Diabetic Atherogenesis
DR Beriault, GH Werstuck
Experimental Diabetes Research 2012
O-GlcNAcylation and oxidation of proteins: is signalling in the cardiovascular system becoming sweeter?
VV Lima, K Spitler, H Choi, RC Webb, RC Tostes
Clinical science (London, England : 1979) 2012
Mitochondrial dysfunction and mitochondrial DNA mutations in atherosclerotic complications in diabetes
DA Chistiakov, IA Sobenin, YV Bobryshev, AN Orekhov
World journal of cardiology 2012
Aldolase B Knockdown Prevents High Glucose-Induced Methylglyoxal Overproduction and Cellular Dysfunction in Endothelial Cells
J Liu, TC Mak, A Banigesh, K Desai, R Wang, L Wu
PloS one 2012
Acute Retinal Ischemia Inhibits Endothelium-Dependent Nitric Oxide–Mediated Dilation of Retinal Arterioles via Enhanced Superoxide Production
TW Hein, Y Ren, LB Potts, Z Yuan, E Kuo, RH Rosa, L Kuo
Investigative ophthalmology & visual science 2012
Advanced glycation end products impair the migration, adhesion and secretion potentials of late endothelial progenitor cells
H Li, X Zhang, X Guan, X Cui, Y Wang, H Chu, M Cheng
Cardiovascular Diabetology 2012
Reactive Oxygen and Nitrogen Species in Pathogenesis of Vascular Complications of Diabetes
SM Son
Diabetes & Metabolism Journal 2012
The influence of high glucose on the aerobic metabolism of endothelial EA.hy926 cells
A Koziel, A Woyda-Ploszczyca, A Kicinska, W Jarmuszkiewicz
Pflügers Archiv : European journal of physiology 2012
Diabetes impairs stem cell and proangiogenic cell mobilization in humans
GP Fadini, M Albiero, SV de Kreutzenberg, E Boscaro, R Cappellari, M Marescotti, N Poncina, C Agostini, A Avogaro
Diabetes care 2012
Regulation of endothelial nitric-oxide synthase (NOS) S-glutathionylation by neuronal NOS: evidence of a functional interaction between myocardial constitutive NOS isoforms
WO Idigo, S Reilly, MH Zhang, YH Zhang, R Jayaram, R Carnicer, MJ Crabtree, JL Balligand, B Casadei
The Journal of biological chemistry 2012
Propyl gallate plays a nephroprotective role in early stage of diabetic nephropathy associated with suppression of glomerular endothelial cell proliferation and angiogenesis
S Tian, J Tang, H Liu, L Wang, J Shen, J Li, Y Gan
Experimental Diabetes Research 2012
Vascular effects of intravenous intralipid and dextrose infusions in obese subjects
AR Gosmanov, DD Smiley, L Peng, J Siquiera, G Robalino, C Newton, GE Umpierrez
Metabolism: clinical and experimental 2012
Taurine reduces nitrosative stress and nitric oxide synthase expression in high glucose-exposed human Schwann cells
T Askwith, W Zeng, MC Eggo, MJ Stevens
Experimental Neurology 2012
Diabetic Peripheral Neuropathy: Should a Chaperone Accompany Our Therapeutic Approach?
KL Farmer, C Li, RT Dobrowsky, EE Scott
Pharmacological reviews 2012
Insulin resistance, metabolic stress, and atherosclerosis.
Pansuria M, Xi H, Li L, Yang XF, Wang H
Frontiers in bioscience (Scholar edition) 2012
Comprehensive Physiology
R Terjung
Comprehensive Physiology 2011
Acute regulation of cardiac metabolism by the hexosamine biosynthesis pathway and protein O-GlcNAcylation
B Laczy, N Fülöp, A Onay-Besikci, CD Rosiers, JC Chatham
PloS one 2011
Körperliche Aktivität und endotheliale Dysfunktion bei Typ-2-Diabetikern: über die Rolle von Stickstoffmonoxid und oxidativem Stress
C Brinkmann, RH Schwinger, K Brixius
Wiener Medizinische Wochenschrift 2011
Protein O-linked β-N-acetylglucosamine: A novel effector of cardiomyocyte metabolism and function
VM Darley-Usmar, LE Ball, JC Chatham
Journal of Molecular and Cellular Cardiology 2011
Continuous exposure to l-arginine induces oxidative stress and physiological tolerance in cultured human endothelial cells
S Mohan, CC Wu, S Shin, HL Fung
Amino Acids 2011
Activation of hexosamine pathway impairs nitric oxide (NO)-dependent arteriolar dilations by increased protein O-GlcNAcylation
T Beleznai, Z Bagi
Vascular Pharmacology 2011
Cross Talk Between O-GlcNAcylation and Phosphorylation: Roles in Signaling, Transcription, and Chronic Disease
GW Hart, C Slawson, G Ramirez-Correa, O Lagerlof
Annual Review of Biochemistry 2011
Mitochondrial Dysfunction in Diabetic Cardiomyopathy
JG Duncan
Biochimica et Biophysica Acta 2011
Hyperbaric oxygen – its mechanisms and efficacy
SR Thom
Plastic and Reconstructive Surgery 2011
Endothelial Nitric Oxide Synthase Overexpression Restores the Efficiency of Bone Marrow Mononuclear Cell-Based Therapy
B Mees, A Récalde, C Loinard, D Tempel, M Godinho, J Vilar, R Haperen, B Lévy, R Crom, JS Silvestre
The American Journal of Pathology 2011
Sub-antimicrobial doxycycline for periodontitis reduces hemoglobin A1c in subjects with type 2 diabetes: a pilot study
SP Engebretson, J Hey-Hadavi
Pharmacological research : the official journal of the Italian Pharmacological Society 2011
Is Hyperglycemia a Cardiovascular Risk Factor?
F Pistrosch, A Natali, M Hanefeld
Diabetes care 2011
Altered Mitochondrial Dynamics Contributes to Endothelial Dysfunction in Diabetes Mellitus
SM Shenouda, ME Widlansky, K Chen, G Xu, M Holbrook, CE Tabit, NM Hamburg, AA Frame, TL Caiano, MA Kluge, MA Duess, A Levit, B Kim, ML Hartman, L Joseph, OS Shirihai, JA Vita
Circulation 2011
Chemical Arsenal for the Study of O-GlcNAc
EJ Kim
Molecules (Basel, Switzerland) 2011
CYP2J3 Gene Delivery Reduces Insulin Resistance via Upregulation of eNOS in Fructose-treated Rats
X Xu, L Tu, L Wang, X Fang, DW Wang
Cardiovascular Diabetology 2011
Oxidative stress and diabetic complications
F Giacco, M Brownlee
Circulation research 2010
Adiponectin resistance and vascular dysfunction in the hyperlipidemic state
R Li, WB Lau, XL Ma
Acta Pharmacologica Sinica 2010
Endothelial dysfunction in diabetes: multiple targets for treatment
H Ding, CR Triggle
Pflügers Archiv - European Journal of Physiology 2010
Hyperglycemia in acute ischemic stroke: pathophysiology and clinical management
ND Kruyt, GJ Biessels, JH DeVries, YB Roos
Nature Reviews Neurology 2010
Molecular mechanisms of diabetic vascular complications
M Kitada, Z Zhang, A Mima, GL King
Journal of Diabetes Investigation 2010
O-glycosylation regulates ubiquitination and degradation of the anti-inflammatory protein A20 to accelerate atherosclerosis in diabetic ApoE-null mice
GV Shrikhande, ST Scali, CG da Silva, SM Damrauer, E Csizmadia, P Putheti, M Matthey, R Arjoon, R Patel, JJ Siracuse, ER Maccariello, ND Andersen, T Monahan, C Peterson, S Essayagh, P Studer, RP Guedes, O Kocher, A Usheva, A Veves, E Kaczmarek, C Ferran
PloS one 2010
Altered mitochondrial membrane potential, mass, and morphology in the mononuclear cells of humans with type 2 diabetes
ME Widlansky, J Wang, SM Shenouda, TM Hagen, AR Smith, TJ Kizhakekuttu, MA Kluge, D Weihrauch, DD Gutterman, JA Vita
Translational research : the journal of laboratory and clinical medicine 2010
Rosiglitazone and cognitive stability in older individuals with type 2 diabetes and mild cognitive impairment
AM Abbatecola, F Lattanzio, AM Molinari, M Cioffi, L Mansi, P Rambaldi, L DiCioccio, F Cacciapuoti, R Canonico, G Paolisso
Diabetes care 2010
Mitochondrial respiratory chain dysfunction in dorsal root ganglia of streptozotocin-induced diabetic rats and its correction by insulin treatment
SK Chowdhury, E Zherebitskaya, DR Smith, E Akude, S Chattopadhyay, CG Jolivalt, NA Calcutt, P Fernyhough
Diabetes 2010
ANG II type I receptor antagonism improved nitric oxide production and enhanced eNOS and PKB/Akt expression in hearts from a rat model of insulin resistance
B Huisamen, SJ Pêrel, SO Friedrich, R Salie, H Strijdom, A Lochner
Molecular and Cellular Biochemistry 2010
The paradoxical world of protein O-GlcNAcylation: a novel effector of cardiovascular (dys)function
SA Marsh, JC Chatham
Cardiovascular Research 2010
Knockout of insulin receptors in cardiomyocytes attenuates coronary arterial dysfunction induced by pressure overload
JD Symons, P Hu, Y Yang, X Wang, QJ Zhang, AR Wende, CL Sloan, S Sena, ED Abel, SE Litwin
American journal of physiology. Heart and circulatory physiology 2010
O-GlcNAcylation: a novel pathway contributing to the effects of endothelin in the vasculature
VV Lima, FR Giachini, DM Hardy, RC Webb, RC Tostes
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 2010
Glucosamine Treatment-mediated O-GlcNAc Modification of Paxillin Depends on Adhesion State of Rat Insulinoma INS-1 Cells*
TK Kwak, H Kim, O Jung, SA Lee, M Kang, HJ Kim, JM Park, SH Kim, JW Lee
The Journal of biological chemistry 2010
Dietary hyperglycemia, glycemic index and metabolic retinal diseases
CJ Chiu, A Taylor
Progress in Retinal and Eye Research 2010
Beneficial effect of the oligomerized polyphenol oligonol on high glucose-induced changes in eNOS phosphorylation and dephosphorylation in endothelial cells: Oligonol on eNOS regulation under high glucose
XH Zhang, H Yokoo, H Nishioka, H Fujii, N Matsuda, T Hayashi, Y Hattori
British Journal of Pharmacology 2010
OGA inhibition by GlcNAc-selenazoline
EJ Kim, DC Love, E Darout, M Abdo, B Rempel, SG Withers, PR Rablen, JA Hanover, S Knapp
Bioorganic & Medicinal Chemistry 2010
O-GlcNAc Modification: Friend or Foe in Diabetic Cardiovascular Disease
U Karunakaran, NH Jeoung
Korean Diabetes Journal 2010
Methylglyoxal scavengers attenuate endothelial dysfunction induced by methylglyoxal and high concentrations of glucose: Methylglyoxal and endothelial dysfunction
A Dhar, I Dhar, KM Desai, L Wu
British Journal of Pharmacology 2010
Arginase II Deletion Increases Corpora Cavernosa Relaxation in Diabetic Mice: Arginase II Deletion Improves Erectile Function in Diabetes
HA Toque, RC Tostes, L Yao, Z Xu, RC Webb, RB Caldwell, RW Caldwell
Journal of Sexual Medicine 2010
O -GlcNAc Signaling in the Cardiovascular System
GA Ngoh, HT Facundo, A Zafir, SP Jones
Circulation research 2010
The intersections between O -GlcNAcylation and phosphorylation: implications for multiple signaling pathways
Q Zeidan, GW Hart
Journal of cell science 2010
Protein O-GlcNAcylation: A critical regulator of the cellular response to stress.
Chatham JC, Marchase RB
Current signal transduction therapy 2010
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009
Pathogenesis and pathophysiology of accelerated atherosclerosis in the diabetic heart
A DSouza, M Hussain, FC Howarth, NM Woods, K Bidasee, J Singh
Molecular and Cellular Biochemistry 2009
Role of nitrosative stress in the pathogenesis of diabetic vascular dysfunction
C Szabo
British Journal of Pharmacology 2009
Molecular insights and therapeutic targets for diabetic endothelial dysfunction
J Xu, MH Zou
Circulation 2009
O-GlcNAcylation: a novel post-translational mechanism to alter vascular cellular signaling in health and disease: focus on hypertension
VV Lima, CS Rigsby, DM Hardy, RC Webb, RC Tostes
Journal of the American Society of Hypertension : JASH 2009
The hexosamine signaling pathway: O-GlcNAc cycling in feast or famine
JA Hanover, MW Krause, DC Love
Biochimica et Biophysica Acta 2009
Effects of the Cellcultured Acanthopanax senticosus Extract on Antioxidative Defense System and Membrane Fluidity in the Liver of Type 2 Diabetes Mouse
JH Hong, YS Cha, SJ Rhee
Journal of Clinical Biochemistry and Nutrition 2009
Endothelial inflammation induced by excess glucose is associated with cytosolic glucose 6-phosphate but not increased mitochondrial respiration
IR Sweet, M Gilbert, E Maloney, DM Hockenbery, MW Schwartz, F Kim
Diabetologia 2009
Molecular mechanisms underlying the activation of eNOS
I Fleming
Pflügers Archiv - European Journal of Physiology 2009
Shifting the Disease Management Paradigm From Glucose: What are the cons?
M Hanefeld, SR Bornstein, F Pistrosch
Diabetes care 2009
O-GlcNAc cycling: Implications for neurodegenerative disorders
BD Lazarus, DC Love, JA Hanover
The International Journal of Biochemistry & Cell Biology 2009
Impaired Vasodilator Activity in Deoxycorticosterone Acetate-Salt Hypertension Is Associated With Increased Protein O-GlcNAcylation
VV Lima, FR Giachini, H Choi, FS Carneiro, ZN Carneiro, ZB Fortes, MH Carvalho, RC Webb, RC Tostes
Hypertension 2009
Regulation of Calcium/Calmodulin-dependent Kinase IV by O-GlcNAc Modification
WB Dias, WD Cheung, Z Wang, GW Hart
The Journal of biological chemistry 2009
O-linked β-N-acetylglucosamine during hyperglycemia exerts both anti-inflammatory and pro-oxidative properties in the endothelial system
Rajapakse AG, Ming XF, Carvas JM, Yang Z
Oxidative medicine and cellular longevity 2009
Oxidative stress as a mediator of cardiovascular disease.
Elahi MM, Kong YX, Matata BM
Oxidative medicine and cellular longevity 2009
Therapeutic interventions and oxidative stress in diabetes.
Rahangdale S, Yeh SY, Malhotra A, Veves A
2009
Oxidative stress is fundamental to hyperbaric oxygen therapy
SR Thom
Journal of applied physiology 2008
Decreasing intracellular superoxide corrects defective ischemia-induced new vessel formation in diabetic mice
DJ Ceradini, D Yao, RH Grogan, MJ Callaghan, D Edelstein, M Brownlee, GC Gurtner
The Journal of biological chemistry 2008
Effects of glucose tolerance on the changes provoked by glucose ingestion in microvascular function
A Natali, S Baldi, F Vittone, E Muscelli, A Casolaro, C Morgantini, C Palombo, E Ferrannini
Diabetologia 2008
Mechanisms underlying recoupling of eNOS by HMG-CoA reductase inhibition in a rat model of streptozotocin-induced diabetes mellitus
P Wenzel, A Daiber, M Oelze, M Brandt, E Closs, J Xu, T Thum, J Bauersachs, G Ertl, MH Zou, U Förstermann, T Münzel
Atherosclerosis 2008
An Integrated View of Insulin Resistance and Endothelial Dysfunction
R Muniyappa, M Iantorno, MJ Quon
Endocrinology & Metabolism Clinics of North America 2008
Heightened efficacy of nitric oxide-based therapies in type II diabetes mellitus and metabolic syndrome
SS Ahanchi, VN Varu, ND Tsihlis, J Martinez, CG Pearce, MR Kapadia, Q Jiang, JE Saavedra, LK Keefer, JA Hrabie, MR Kibbe
American journal of physiology. Heart and circulatory physiology 2008
Increased vascular O-GlcNAcylation augments reactivity to constrictor stimuli - VASOACTIVE PEPTIDE SYMPOSIUM
VV Lima, FR Giachini, FS Carneiro, ZN Carneiro, ZB Fortes, MH Carvalho, RC Webb, RC Tostes
Journal of the American Society of Hypertension : JASH 2008
Protein O-GlcNAcylation: a new signaling paradigm for the cardiovascular system
B Laczy, BG Hill, K Wang, AJ Paterson, CR White, D Xing, YF Chen, V Darley-Usmar, S Oparil, JC Chatham
American journal of physiology. Heart and circulatory physiology 2008
What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium?
SC Satchell, JE Tooke
Diabetologia 2008
Aging leads to increased levels of protein O-linked N-acetylglucosamine in heart, aorta, brain and skeletal muscle in Brown-Norway rats
N Fülöp, W Feng, D Xing, K He, LG Not, CA Brocks, RB Marchase, AP Miller, JC Chatham
Biogerontology 2008
Epidemic inflammation: pondering obesity
C Nathan
Molecular Medicine 2008
Mechanisms of high-glucose/insulin-mediated desensitization of acute insulin-stimulated glucose transport and Akt activation
KA Robinson, MG Buse
American journal of physiology. Endocrinology and metabolism 2008
Cross-talk between GlcNAcylation and phosphorylation: roles in insulin resistance and glucose toxicity
RJ Copeland, JW Bullen, GW Hart
American journal of physiology. Endocrinology and metabolism 2008
Rho Kinase Inhibition by Fasudil Ameliorates Diabetes-Induced Microvascular Damage
R Arita, Y Hata, S Nakao, T Kita, M Miura, S Kawahara, S Zandi, L Almulki, F Tayyari, H Shimokawa, A Hafezi-Moghadam, T Ishibashi
Diabetes 2008
Effects of α-lipoic acid on endothelial function in aged diabetic and high-fat fed rats: Attenuation of endothelial dysfunction by α-LA
CM Sena, E Nunes, T Louro, T Proença, R Fernandes, MR Boarder, RM Seiça
British Journal of Pharmacology 2008
Simvastatin Restores Ischemic Preconditioning in the Presence of Hyperglycemia through a Nitric Oxide–mediated Mechanism:
W Gu, F Kehl, JG Krolikowski, PS Pagel, DC Warltier, JR Kersten
Anesthesiology 2008
Reduced Expression of ATP-Binding Cassette Transporter G1 Increases Cholesterol Accumulation in Macrophages of Patients With Type 2 Diabetes Mellitus
JP Mauldin, MH Nagelin, AJ Wojcik, S Srinivasan, MD Skaflen, CR Ayers, CA McNamara, CC Hedrick
Circulation 2008
Protein Modification by O-Linked GlcNAc Reduces Angiogenesis by Inhibiting Akt Activity in Endothelial Cells
B Luo, Y Soesanto, DA McClain
Arteriosclerosis, thrombosis, and vascular biology 2008
Overexpression of Calmodulin in Pancreatic β Cells Induces Diabetic Nephropathy
Y Yuzawa, I Niki, T Kosugi, S Maruyama, F Yoshida, M Takeda, Y Tagawa, Y Kaneko, T Kimura, N Kato, J Yamamoto, W Sato, T Nakagawa, S Matsuo
Journal of the American Society of Nephrology : JASN 2008
Bidirectional Actions of Hydrogen Peroxide on Endothelial Nitric-oxide Synthase Phosphorylation and Function
Z Hu, J Chen, Q Wei, Y Xia
The Journal of biological chemistry 2008
AMP-activated Protein Kinase and p38 MAPK Activate O -GlcNAcylation of Neuronal Proteins during Glucose Deprivation
WD Cheung, GW Hart
The Journal of biological chemistry 2008
Diabetic impairments in NO-mediated endothelial progenitor-cell mobilization and homing are reversed by hyperoxia and SDF-1alpha
Katherine A. Gallagher, M.D., Zhao-Jun Liu, M.D. Ph.D., Min Xiao, M.D, Haiying Chen, M.D., Lee J. Goldstein, M.D., Donald G. Buerk, Ph.D., April Nedeau, M.D., Stephen R. Thom, M.D., Ph.D., Omaida C. Velazquez, M.D.
Journal of Clinical Investigation 2007
Chronic hyperglicemia and nitric oxide bioavailability play a pivotal role in pro-atherogenic vascular modifications
A Pandolfi, EA de Filippis
Genes & Nutrition 2007
Insulin reduces plasma arginase activity in type 2 diabetic patients
SR Kashyap, A Lara, R Zhang, YM Park, RA DeFronzo
Diabetes care 2007
Life history of eNOS: partners and pathways
DM Dudzinski, T Michel
Cardiovascular Research 2007
Insulin enhances nitric oxide production in trabecular meshwork cells via de novo pathway for tetrahydrobiopterin synthesis
JW Kim
Korean journal of ophthalmology : KJO 2007
Mechanisms by which diabetes increases cardiovascular disease
CA Gleissner, E Galkina, JL Nadler, K Ley
Drug discovery today. Disease mechanisms 2007
The endothelial glycocalyx: composition, functions, and visualization
S Reitsma, DW Slaaf, H Vink, MA van Zandvoort, MG Egbrink
Pflügers Archiv : European journal of physiology 2007
Resistance to high-fat-diet-induced obesity and sexual dimorphism in the metabolic responses of transgenic mice with moderate uncoupling protein 3 overexpression in glycolytic skeletal muscles
C Tiraby, G Tavernier, F Capel, A Mairal, F Crampes, J Rami, C Pujol, JA Boutin, D Langin
Diabetologia 2007
Antioxidants and CVD in Diabetes: Where Do We Stand Now?
Yim S, Malhotra A, Veves A
Current Diabetes Reports 2007
Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation
Xueliang Du, Diane Edelstein, Silvana Obici, Ninon Higham, Ming-Hui Zou, and Michael Brownlee
Journal of Clinical Investigation 2006
Benfotiamine accelerates the healing of ischaemic diabetic limbs in mice through protein kinase B/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis
S Gadau, C Emanueli, S Linthout, G Graiani, M Todaro, M Meloni, I Campesi, G Invernici, F Spillmann, K Ward, P Madeddu
Diabetologia 2006
Role of protein O-linked N-acetyl-glucosamine in mediating cell function and survival in the cardiovascular system
N Fülöp, RB Marchase, JC Chatham
Cardiovascular Research 2006
Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology
T Yu, JL Robotham, Y Yoon
Proceedings of the National Academy of Sciences 2006
NO-mediated regulation of NAD(P)H oxidase by laminar shear stress in human endothelial cells: Regulation of NAD(P)H oxidase by shear stress
N Duerrschmidt, C Stielow, G Muller, PJ Pagano, H Morawietz
The Journal of Physiology 2006
Oxidative stress in type 2 diabetes: the role of fasting and postprandial glycaemia: Oxidative Stress in Type 2 Diabetes
E Wright, JL Scism-Bacon, LC Glass
International journal of clinical practice. Supplement 2006
Recent advances in understanding endothelial dysfunction in atherosclerosis.
Yang Z, Ming XF
Clinical medicine & research 2006
Introduction of hyperglycemia and dyslipidemia in the pathogenesis of diabetic vascular complications
Y Xu, Z He, GL King
Current Diabetes Reports 2005
Inactivation of phosphorylated endothelial nitric oxide synthase (Ser-1177) by O-GlcNAc in diabetes-associated erectile dysfunction
B Musicki, MF Kramer, RE Becker, AL Burnett
Proceedings of the National Academy of Sciences 2005
Myocardial angiogenesis
E Toyota, T Matsunaga, WM Chilian
Molecular and Cellular Biochemistry 2004
Hyperglycaemia-induced superoxide production decreases eNOS expression via AP-1 activation in aortic endothelial cells
S Srinivasan, ME Hatley, DT Bolick, LA Palmer, D Edelstein, M Brownlee, CC Hedrick
Diabetologia 2004
Posttranslational regulation of NO synthase activity in the renal medulla of diabetic rats
DL Lee, JM Sasser, JL Hobbs, A Boriskie, DM Pollock, PK Carmines, JS Pollock
American journal of physiology. Renal physiology 2004
Nitric oxide, oxidative excess, and vascular complications of diabetes mellitus
DH Endemann, EL Schiffrin
Current Hypertension Reports 2004
Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells
Xueliang Du, Takeshi Matsumura, Diane Edelstein, Luciano Rossetti, Zsuzsanna Zsengeller, Csaba Szabo, Michael Brownlee
Journal of Clinical Investigation 2003
Endothelial nitric oxide synthase and endothelial dysfunction
PL Huang
Current Hypertension Reports 2003
Altered glycan-dependent signaling induces insulin resistance and hyperleptinemia
DA McClain, WA Lubas, RC Cooksey, M Hazel, GJ Parker, DC Love, JA Hanover
Proceedings of the National Academy of Sciences 2002
Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection
KJ Hurt, B Musicki, MA Palese, JK Crone, RE Becker, JL Moriarity, SH Snyder, AL Burnett
Proceedings of the National Academy of Sciences 2002
Mechanisms involved in platelet hyperactivation and platelet-endothelium interrelationships in diabetes mellitus
M Trovati, G Anfossi
Current Diabetes Reports 2002
More sweetness than light? A search for the causes of diabetic vasculopathy
Junsuke Igarashi, Tom Michel
Journal of Clinical Investigation 2001

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