Cited by 205Nitric Oxide and Endothelin EffectsMetabolism, Diabetes, and CancerDiabetes Treatment and Management

The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.

Metformin decreases intracellular production of reactive oxygen species in aortic endothelial cells

Ouslimani, Nadjat, Peynet, Jacqueline, Bonnefont-Rousselot, Dominique, Thérond, Patrice, Legrand, Alain, Beaudeux, Jean-Louis·2005·Metabolism

DOI 10.1016/j.metabol.2005.01.029

Open this paper in CoChat — free account

Abstract

Beyond its antidiabetic activity justifying its use in the treatment of the type 2 diabetes, metformin (MET [dimethylguanidine, Glucophage]) has been shown to exhibit antioxidant properties in vitro, which could contribute to limit the deleterious vascular complications of diabetes. We investigated whether MET, at the pharmacological level of 10 -5 mol/L, was able to modulate intracellular production of reactive oxygen species (ROS) both in quiescent bovine aortic endothelial cells (BAECs) and in BAECs stimulated by a short incubation with high levels of glucose (30 mmol/L, 2 hours) or angiotensin II (10 -7 mol/L, 1 hour). Intracellular ROS production was measured by fluorescence of the DCF (2,7-dichlorodihydrofluorescein) probe. Our results showed that MET was able to reduce the intracellular production of ROS in both nonstimulated BAECs (-20%, P < .05) and BAEC stimulated by high levels of glucose or angiotensin II (-28% and -72%, respectively, P < .01). Experiments performed in the presence of the nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase inhibitor apocynin or the respiratory mitochondrial chain inhibitor rotenone indicated that MET exerted its effect partly through an inhibition of the formation of ROS produced mainly by NAD(P)H oxidase and also, to a lesser extent, by the respiratory mitochondrial chain.

Integrity signals

Registry

Crossref · 10.1016/j.metabol.2005.01.029

Cites

54 of 54 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

1 retracted

Activation of the AMP-activated Protein Kinase by the Anti-diabetic Drug Metformin in Vivo
Zou, M., Kirkpatrick, S. S., Davis, B. J., Nelson, J. S., Wiles, W. G., Schlattner, U., Neumann, D., Brownlee, M., Freeman, M. B., & Goldman, M. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404421200 · Cited by 480
Retracted
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)
(1998) · The Lancet · doi:10.1016/s0140-6736(98)07037-8 · Cited by 8,247
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
Nishikawa, T., Edelstein, D., Du, X. L., Yamagishi, S.-I., Matsumura, T., Kaneda, Y., Yorek, M. A., Beebe, D., Oates, P. J., Hammes, H.-P., et al. (2000) · Nature · doi:10.1038/35008121 · Cited by 4,277
Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?
Halliwell, B., & Whiteman, M. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705776 · Cited by 2,238
Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes
Evans, J. L., Goldfine, I. D., Maddux, B. A., & Grodsky, G. M. (2002) · Endocrine Reviews · doi:10.1210/er.2001-0039 · Cited by 2,232
High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells
Inoguchi, T., Li, P., Umeda, F., Yu, H. Y., Kakimoto, M., Imamura, M., Aoki, T., Etoh, T., Hashimoto, T., Naruse, M., et al. (2000) · Diabetes · doi:10.2337/diabetes.49.11.1939 · Cited by 1,577
The role of oxidized lipoproteins in atherogenesis
Berliner, J. A., & Heinecke, J. W. (1996) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(95)02173-6 · Cited by 1,369
Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins
Yan, S. D., Schmidt, A. M., Anderson, G. M., Zhang, J., Brett, J., Zou, Y., Pinsky, D. J., & Stern, D. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36966-1 · Cited by 1,305
Role of oxidative stress in atherosclerosis
Harrison, D., Griendling, K. K., Landmesser, U., Hornig, B., & Drexler, H. (2003) · The American Journal of Cardiology · doi:10.1016/s0002-9149(02)03144-2 · Cited by 1,275
Metformin: An Update
Kirpichnikov, D., McFarlane, S. I., & Sowers, J. R. (2002) · Annals of Internal Medicine · doi:10.7326/0003-4819-137-1-200207020-00009 · Cited by 1,084
Metformin Increases AMP-Activated Protein Kinase Activity in Skeletal Muscle of Subjects With Type 2 Diabetes
Musi, N., Hirshman, M. F., Nygren, J., Svanfeldt, M., Bavenholm, P., Rooyackers, O., Zhou, G., Williamson, J. M., Ljunqvist, O., Efendic, S., et al. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2074 · Cited by 806
Angiotensin II Stimulation of NAD(P)H Oxidase Activity
Seshiah, P., Weber, D. S., Ročić, P., Valppu, L., Taniyama, Y., & Griendling, K. K. (2002) · Circulation Research · doi:10.1161/01.res.0000033523.08033.16 · Cited by 711
Intracellular hydrogen peroxide and superoxide anion detection in endothelial cells
Carter, W. O., Narayanan, P. K., & Robinson, J. P. (1994) · Journal of Leukocyte Biology · doi:10.1002/jlb.55.2.253 · Cited by 640
How hyperglycemia promotes atherosclerosis: molecular mechanisms
Aronson, D., & Rayfield, E. J. (2002) · Cardiovascular Diabetology · doi:10.1186/1475-2840-1-1 · Cited by 520
Decreased Mortality Associated With the Use of Metformin Compared With Sulfonylurea Monotherapy in Type 2 Diabetes
Johnson, J. A., Majumdar, S. R., Simpson, S. H., & Toth, E. L. (2002) · Diabetes Care · doi:10.2337/diacare.25.12.2244 · Cited by 421
The Antihyperglycaemic Effect of Metformin
Wiernsperger, N. F., & Bailey, C. J. (1999) · Drugs · doi:10.2165/00003495-199958001-00009 · Cited by 320
Mechanism of Endothelial Cell NADPH Oxidase Activation by Angiotensin II
Li, J., & Shah, A. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209793200 · Cited by 307
Angiotensin II-induced superoxide anion generation in human vascular endothelial cells Role of membrane-bound NADH-/NADPH-oxidases
Zhang, H. (1999) · Cardiovascular Research · doi:10.1016/s0008-6363(99)00183-2 · Cited by 296
Oxidation pathways for the intracellular probe 2′,7′-dichlorofluorescin
Zhu, H., Bannenberg, G. L., Moldéus, P., & Shertzer, H. G. (1994) · Archives of Toxicology · doi:10.1007/s002040050118 · Cited by 261
Dose-Dependent Regulation of NAD(P)H Oxidase Expression by Angiotensin II in Human Endothelial Cells: Protective Effect of Angiotensin II Type 1 Receptor Blockade in Patients With Coronary Artery Disease
Rueckschloss, U., Quinn, M. T., Holtz, J., & Morawietz, H. (2002) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000035392.38687.65 · Cited by 216
Defective intracellular antioxidant enzyme production in type 1 diabetic patients with nephropathy.
Ceriello, A., Morocutti, A., Mercuri, F., Quagliaro, L., Moro, M., Damante, G., & Viberti, G. C. (2000) · Diabetes · doi:10.2337/diabetes.49.12.2170 · Cited by 209
NAD(P)H Oxidase-derived Hydrogen Peroxide Mediates Endothelial Nitric Oxide Production in Response to Angiotensin II
Cai, H. “., Li, Z., Dikalov, S., Holland, S. M., Hwang, J., Jo, H., Dudley, S. C., & Harrison, D. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208884200 · Cited by 182
Oxidative stress in cardiovascular disease: myth or fact?
Ceconi, C., Boraso, A., Cargnoni, A., & Ferrari, R. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.06.002 · Cited by 170
An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats.
Faure, P., Rossini, E., Wiernsperger, N., Richard, M. J., Favier, A., & Halimi, S. (1999) · Diabetes · doi:10.2337/diabetes.48.2.353 · Cited by 166
Oxidative Stress–Induced Iron Signaling Is Responsible for Peroxide-Dependent Oxidation of Dichlorodihydrofluorescein in Endothelial Cells
Tampo, Y., Kotamraju, S., Chitambar, C. R., Kalivendi, S. V., Keszler, Á., Joseph, J., & Kalyanaraman, B. (2003) · Circulation Research · doi:10.1161/01.res.0000048195.15637.ac · Cited by 164
An intracellular modulation of free radical production could contribute to the beneficial effects of metformin towards oxidative stress
Bonnefont‐Rousselot, D., Raji, B., Walrand, S., Gardès-Albert, M., Jore, D., Legrand, A., Peynet, J., & Vasson, M. (2003) · Metabolism · doi:10.1053/meta.2003.50093 · Cited by 162
Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus
Abbasi, F., Chu, J. W., McLaughlin, T., Lamendola, C. A., Leary, E. T., & Reaven, G. M. (2004) · Metabolism · doi:10.1016/j.metabol.2003.07.020 · Cited by 162
Evidence for a role of Trp proteins in the oxidative stress-induced membrane conductances of porcine aortic endothelial cells
Balzer, M. (1999) · Cardiovascular Research · doi:10.1016/s0008-6363(99)00025-5 · Cited by 152
Vascular targets of redox signalling in diabetes mellitus
Spitaler, M. M., & Graier, W. F. (2002) · Diabetologia · doi:10.1007/s00125-002-0782-0 · Cited by 149
Mitochondrial metabolism and type-2 diabetes: a specific target of metformin
Leverve, X. M., Guigas, B., Détaille, D., Batandier, C., Koceir, E.-A., Chauvin, C., Fontaine, E. M., & Wiernsperger, N. F. (2003) · Diabetes & Metabolism · doi:10.1016/s1262-3636(03)72792-x · Cited by 132
Senescence-associated cell death of human endothelial cells: the role of oxidative stress
Unterluggauer, H. (2003) · Experimental Gerontology · doi:10.1016/j.exger.2003.08.007 · Cited by 121
Intimal redox stress: Accelerated atherosclerosis in metabolic syndrome and type 2 diabetes mellitus. Atheroscleropathy
Hayden, M. R., & Tyagi, S. C. (2002) · Cardiovascular Diabetology · doi:10.1186/1475-2840-1-3 · Cited by 115
Effect of four‐week metformin treatment on plasma and erythrocyte antioxidative defense enzymes in newly diagnosed obese patients with type 2 diabetes
Pavlovic, D. D., Kocić, R., Kocic, G. M., Jevtović, T., Radenković, S., Mikić, D., Stojanović, M., & Djordjević, P. (2000) · Diabetes Obesity and Metabolism · doi:10.1046/j.1463-1326.2000.00089.x · Cited by 113
tert -Butyl hydroperoxide-induced lipid signaling in hepatocytes: involvement of glutathione and free radicals 1 1Abbreviations: [14C]-AA, [14C]-arachidonic acid; DCF, 2′,7′-dichlorofluorescein; DCFDA, 2′,7′-dichlorofluorescin diacetate; DTT, 1,4-dithiothreitol; MDA, malondialdehyde; PLA2, phospholipase A2; ROS, reactive oxygen species; TBARS, thiobarbituric acid reactive substances; and TBHP, tert-butyl hydroperoxide.
Martı́n, C., Martı́nez, R., Navarro, R., Ruiz-Sanz, J. I., Lacort, M., & Ruiz‐Larrea, M. B. (2001) · Biochemical Pharmacology · doi:10.1016/s0006-2952(01)00704-3 · Cited by 112
Chemically de-acetylated 2′,7′-dichlorodihydrofluorescein diacetate as a probe of respiratory burst activity in mononuclear phagocytes
Brubacher, J. L., & Bols, N. C. (2001) · Journal of Immunological Methods · doi:10.1016/s0022-1759(01)00308-8 · Cited by 102
Impaired Activation of Glucose Oxidation and NADPH Supply in Human Endothelial Cells Exposed to H2O2 in High-Glucose Medium
Asahina, T., Kashiwagi, A., Nishio, Y., Ikebuchi, M., Harada, N., Tanaka, Y., Takagi, Y., Saeki, Y., Kikkawa, R., & Shigeta, Y. (1995) · Diabetes · doi:10.2337/diab.44.5.520 · Cited by 102
Obligatory role of membrane events in the regulatory effect of metformin on the respiratory chain function
Détaille, D., Guigas, B., Leverve, X. M., Wiernsperger, N. F., & Devos, P. E. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)00858-4 · Cited by 100
Effect of metformin on glutathione and magnesium in normal and streptozotocin‐induced diabetic rats
Ewis, S. A., & Abdel‐Rahman, M. S. (1995) · Journal of Applied Toxicology · doi:10.1002/jat.2550150508 · Cited by 98
Effects of metformin on tyrosine kinase activity, glucose transport, and intracellular calcium in rat vascular smooth muscle
Dominguez, L. J., Davidoff, A. J., Srinivas, P. R., Standley, P. R., Walsh, M. F., & Sowers, J. R. (1996) · Endocrinology · doi:10.1210/endo.137.1.8536601 · Cited by 87 · cited 1×
“To exert its antihyperglycemic effect, MET was shown to enhance cellular insulin signaling, in part by enhancing the decrease in cyclic (c)AMP levels induced by insulin [46], by increasing tyrosine kinase activity [47,48], as well as by decreasing tyrosine phosphatase activity [49], in relation to the modulation of ce…”
Background
Short-term exposure of high glucose concentration induces generation of reactive oxygen species in endothelial cells: implication for the oxidative stress associated with postprandial hyperglycemia
Yano, M., Hasegawa, G., Ishii, M., Yamasaki, M., Fukui, M., Nakamura, N., & Yoshikawa, T. (2004) · Redox Report · doi:10.1179/135100004225004779 · Cited by 85
Effects of gliclazide versus metformin on the clinical profile and lipid peroxidation markers in type 2 diabetes
Tessier, D., Maheux, P., Khalil, A., & Fülöp, T. (1999) · Metabolism · doi:10.1016/s0026-0495(99)90226-3 · Cited by 84
Endothelial dysfunction in acute and chronic coronary syndromes: evidence for a pathogenetic role of oxidative stress
Valgimigli, M., Merli, E., Malagutti, P., Soukhomovskaia, O., Cicchitelli, G., Macrı̀, G., & Ferrari, R. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.07.006 · Cited by 82
Glycation, Oxidative Stress, and Scavenger Activity: Glucose Metabolism and Radical Scavenger Dysfunction in Endothelial Cells
Kashiwagi, A., Asahina, T., Nishio, Y., Ikebuchi, M., Tanaka, Y., Kikkawa, R., & Shigeta, Y. (1996) · Diabetes · doi:10.2337/diab.45.3.s84 · Cited by 82
Microcirculation in insulin resistance and diabetes: more than just a complication
Wiernsperger, N. F., & Bouskela, E. (2003) · Diabetes & Metabolism · doi:10.1016/s1262-3636(03)72791-8 · Cited by 68
Antidiabetic and antimalarial biguanide drugs are metal-interactive antiproteolytic agents
Sweeney, D., Raymer, M. L., & Lockwood, T. D. (2003) · Biochemical Pharmacology · doi:10.1016/s0006-2952(03)00338-1 · Cited by 66
Metformin (Glucophage) inhibits tyrosine phosphatase activity to stimulate the insulin receptor tyrosine kinase
Holland, W. L., Morrison, T. E., Chang, Y., Wiernsperger, N., & Stith, B. J. (2004) · Biochemical Pharmacology · doi:10.1016/j.bcp.2004.02.016 · Cited by 57
Monotherapy with Metformin: Does It Improve Hypoxia in Type 2 Diabetic Patients?
Ćosić, V., Antić, S., Pesić, M., Jovanović, O., Kundalić, S., & Djordjević, V. B. (2001) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2001.135 · Cited by 38
Impaired activation of glucose oxidation and NADPH supply in human endothelial cells exposed to H2O2 in high-glucose medium
Asahina, T., Kashiwagi, A., Nishio, Y., et al. (1995) · Diabetes · doi:10.2337/diabetes.44.5.520 · Cited by 37
Protection from Cytotoxic Effects Induced by the Nitrogen Mustard Mechlorethamine on Human Bronchial Epithelial Cells in Vitro
Rappeneau, S. (2000) · Toxicological Sciences · doi:10.1093/toxsci/54.1.212 · Cited by 33
Use of Fluorescent Probes to Assess the Early Sulfhydryl Depletion and Oxidative Stress Induced by Mechlorethamine in Human Bronchial Epithelial Cells
Rappeneau, S., Baeza‐Squiban, A., Braut‐Boucher, F., Aubery, M., Gendron, M. C., & Marano, F. (1999) · Toxicology in Vitro · doi:10.1016/s0887-2333(99)00042-9 · Cited by 14
Cellular mechanism of metformin action.
Grigorescu, F., Laurent, A., Chavanieu, A., & Capony, J. (1991) · PubMed · Cited by 13
Potentiating effect of metformin on insulin-induced glucose uptake and glycogen metabolism within Xenopus oocytes
Détaille, D., Wiernsperger, N. F., & Devos, P. (1998) · Diabetologia · doi:10.1007/s001250050859 · Cited by 12
Cellular and molecular mechanisms involved in insulin’s potentiation of glycogen synthase activity by metformin
Détaille, D., Wiernsperger, N. F., & Devos, P. (1999) · Biochemical Pharmacology · doi:10.1016/s0006-2952(99)00222-1 · Cited by 11

Research works printed but not linked: 1

Martin, 2001, tert-Butyl hydroperoxide–induced lipid signaling in hepatocytes: involvement of glutathione and free radicals, Biochem Pharmacol, 62, 705

Sorted by citations

Cellular and molecular mechanisms of metformin: an overview
Viollet, B., Guigas, B., Garcia, N. S., Leclerc, J., Foretz, M., & Andreelli, F. (2012) · Clinical Science · doi:10.1042/cs20110386 · Cited by 1,720
Metformin: from mechanisms of action to therapies
Foretz, M., Guigas, B., Bertrand, L., Pollak, M., & Viollet, B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.09.018 · Cited by 1,501
A review on the role of antioxidants in the management of diabetes and its complications
Rahimi, R., Nikfar, S., Larijani, B. A., & Abdollahi, M. R. (2005) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2005.07.002 · Cited by 890
Molecular mechanism of action of metformin: old or new insights?
Rena, G., Pearson, E. R., & Sakamoto, K. (2013) · Diabetologia · doi:10.1007/s00125-013-2991-0 · Cited by 479
Metformin and inflammation: its potential Beyond glucose-lowering effect
Saisho, Y. (2015) · Endocrine, Metabolic & Immune Disorders-Drug Targets · doi:10.2174/1871530315666150316124019 · Cited by 450

See all 205

Authors: Ouslimani, N., Peynet, J., Bonnefont-Rousselot, D., Thérond, P., Legrand, A., & Beaudeux, J.-L.
Corresponding author: Beaudeux, Jean-Louis
ORCID: Thérond, Patrice
Beaudeux, Jean-Louis
Venue: Metabolism
Publisher: Elsevier BV
Published: 2005-06
Volume: 54
Issue: 6
Pages: 829-834
ISSN: 0026-0495 (ISSN-L)
DOI: 10.1016/j.metabol.2005.01.029
OpenAlex: W2103676852
Cited by: 204
References: 54
Citations by year: 2026: 5 · 2025: 5 · 2024: 8 · 2023: 5 · 2022: 6 · 2021: 20 · 2020: 14 · 2019: 10 · 2018: 9 · 2017: 9 · 2016: 15 · 2015: 13 · 2014: 11 · 2013: 12 · 2012: 11
FWCI: 4.60
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Metabolism (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: metformin, reactive oxygen species, aortic endothelial cells, antioxidant activity, NADPH oxidase, apocynin, mitochondrial respiratory chain, angiotensin II, high glucose, diabetic vascular complications, type 2 diabetes
MeSH terms: Animals, Aorta, Cattle, Cells, Cultured, Hypoglycemic Agents, Metformin, Reactive Oxygen Species, NADPH Oxidases, Endothelial Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Metformin decreases intracellular production of reactive oxygen species in aortic endothelial cells

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks