The DOI matches its Crossref record; 152 of the 152 references it cites were found in a registry or an index.
Oxidative Stress and Diabetic Complications
Open accessAbstract
Oxidative stress plays a pivotal role in the development of diabetes complications, both microvascular and cardiovascular. The metabolic abnormalities of diabetes cause mitochondrial superoxide overproduction in endothelial cells of both large and small vessels, as well as in the myocardium. This increased superoxide production causes the activation of 5 major pathways involved in the pathogenesis of complications: polyol pathway flux, increased formation of AGEs (advanced glycation end products), increased expression of the receptor for AGEs and its activating ligands, activation of protein kinase C isoforms, and overactivity of the hexosamine pathway. It also directly inactivates 2 critical antiatherosclerotic enzymes, endothelial nitric oxide synthase and prostacyclin synthase. Through these pathways, increased intracellular reactive oxygen species (ROS) cause defective angiogenesis in response to ischemia, activate a number of proinflammatory pathways, and cause long-lasting epigenetic changes that drive persistent expression of proinflammatory genes after glycemia is normalized (“hyperglycemic memory”). Atherosclerosis and cardiomyopathy in type 2 diabetes are caused in part by pathway-selective insulin resistance, which increases mitochondrial ROS production from free fatty acids and by inactivation of antiatherosclerosis enzymes by ROS. Overexpression of superoxide dismutase in transgenic diabetic mice prevents diabetic retinopathy, nephropathy, and cardiomyopathy. The aim of this review is to highlight advances in understanding the role of metabolite-generated ROS in the development of diabetic complications.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Chronic overproduction of ROS increases oxidative stress, damages DNA, increases apoptosis, and triggers inflammation, which is a key feature in T2DM and metabolic syndrome (42).”
From TFAM Enhances Fat Oxidation and Attenuates High-Fat Diet–Induced Insulin Resistance in Skeletal Muscle (2019) · cites this paper as [42]
Experimental — accuracy not yet measuredIn the citing paper
“Taken together, our data suggest significant molecular and metabolic perturbations between NHOs and PGDHOs consistent with previous studies on PGD suggesting increased oxidative stress, cardiomyopathy, and altered lipid profiles48–50”
From Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease (2021) · cites this paper as [49]
In the citing paper
“Hyperglycemia and PKC activation-induced ROS production result in inflammatory changes in the vascular endothelium including monocytes adhesion, formation of foam cells, and activation of major biochemical paths including polyol pathway flux and increased formation of advanced glycation end products, further contributing to the development of atherosclerosis.40”
From Glycemic variability and cardiovascular disease in patients with type 2 diabetes (2021) · cites this paper as [40]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
2 retracted
Xie, Z., Zhang, J., Wu, J., Viollet, B., & Zou, M. (2008) · Diabetes · doi:10.2337/db08-0610 · Cited by 165
RetractedReddy, M. A., Villeneuve, L. M., Wang, M., Lanting, L. L., & Natarajan, R. D. (2008) · Circulation Research · doi:10.1161/circresaha.108.175190 · Cited by 83
Retracted(1993) · New England Journal of Medicine · doi:10.1056/nejm199309303291401 · Cited by 24,667
Turner, R. C., Fox, C., Matthews, McElroy, H. H., Cull, C. A., Holman, R. R., Neil, P., Hadden, D. R., Wright, D., Manley, E., et al. (1998) · The Lancet · Cited by 8,419
10-year follow-up of intensive glucose control in type 2 diabetes
Holman, R. R., Paul, S. K., Bethel, M. A., Matthews, D. R., & Neil, H. A. W. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0806470 · Cited by 7,751
Haffner, S. M., Lehto, S., Rönnemaa, T., Pyörälä, K., & Laakso, M. (1998) · New England Journal of Medicine · doi:10.1056/nejm199807233390404 · Cited by 7,000
The Pathobiology of Diabetic Complications
Brownlee, M. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1615 · Cited by 5,339
Self-citationIntensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes
(2005) · New England Journal of Medicine · doi:10.1056/nejmoa052187 · Cited by 5,138
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
Self-citation
Research works printed but not linked: 1
- National Diabetes Data Group. Diabetes in America. 2nd ed. Bethesda, Md: National Institute of Diabetes and Digestive and Kidney Diseases, NIH; 1995.
Cited by
Sorted by citations
Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling
Ray, P. D., Huang, B.-W., & Tsuji, Y. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.01.008 · Cited by 4,373
Pathophysiology of type 2 diabetes mellitus
Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K. B., Ostolaza, H., & Martín, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176275 · Cited by 3,360
“Through these pathways, increased intracellular ROS causes defective angiogenesis in response to ischemia, activates a number of proinflammatory pathways, and cause long-lasting epigenetic changes which drive persistent expression of proinflammatory genes even after glycemia is normalized [58].”
BackgroundDeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J., Hu, F. B., Kahn, C. R., Raz, I., Shulman, G. I., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.19 · Cited by 2,611
Association between insulin resistance and the development of cardiovascular disease
Ormazábal, V., Nair, S., Elfeky, O. W. M., Aguayo, C. R., Salomón, C., & Zuñiga, F. A. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0762-4 · Cited by 2,432
Mechanisms of DNA damage, repair, and mutagenesis
Chatterjee, N., & Walker, G. C. (2017) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22087 · Cited by 2,039
Metadata
- Authors
- Giacco, F., & Brownlee, M.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Brownlee, Michael
- Venue
- Circulation Research
- Published
- 2010-10-29
- Volume
- 107
- Issue
- 9
- Pages
- 1058-1070
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC2996922
- OpenAlex
- W2105731956
- Cited by
- 5,461
- References
- 152
- Citations by year
- 2026: 305 · 2025: 331 · 2024: 416 · 2023: 448 · 2022: 478 · 2021: 435 · 2020: 411 · 2019: 349 · 2018: 370 · 2017: 367 · 2016: 338 · 2015: 318 · 2014: 327 · 2013: 260 · 2012: 203
- FWCI
- 17.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK074153, R01-DK07453, P60DK020541)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- oxidative stress, diabetes complications, superoxide, reactive oxygen species, mitochondrial dysfunction, polyol pathway, advanced glycation end products, AGE receptor, protein kinase C, hexosamine biosynthetic pathway, endothelial nitric oxide synthase, prostacyclin synthase, angiogenesis, inflammation, epigenetic modifications, atherosclerosis, diabetic cardiomyopathy, type 2 diabetes, insulin resistance, superoxide dismutase, diabetic retinopathy, diabetic nephropathy
- MeSH terms
- Animals, Humans, Hyperglycemia, Cardiomyopathies, Signal Transduction, Reactive Oxygen Species, Oxidative Stress, Diabetes Complications, Atherosclerosis, Microvessels
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
