The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats.
Abstract
Recently there has been growing interest in the effects of antioxidants on insulin activity. In the present study, we investigated the effect of metformin on free radical activity and insulin sensitivity in high fructose-fed rats, a diet that leads to insulin resistance. The animals were divided into four groups (n = 16 per group; experiment duration = 6 weeks): the control (C) group received a standard diet; the control metformin (CM) group was fed a control diet and received metformin (200 mg x kg(-1) x day(-1) in water); the fructose control (FT) group was fed a diet in which fructose composed 56.8% of the total carbohydrates; and the fructose metformin (FM) group received high-fructose diet and metformin (200 mg x kg(-1) x day(-1) in water). The glucose clamp technique was used to determine insulin sensitivity in eight animals per group. Metabolic and oxidative stress parameters were measured in the remaining rats. In the FT rats, insulin resistance, lower red cell CuZn superoxide dismutase activity and lower blood reduced glutathione were observed. Metformin treatment improved both the insulin activity and the antioxidant defense system. In the CM group, metformin had no effect on metabolic parameters, but improved red cell antioxidant enzyme activities and the blood GSH level, which suggests that it has an antioxidant activity independent of its effect on insulin activity.
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In the citing paper
“In fact, metformin has recently been reported to have antioxidant effects (34) in addition to the known favorable effects on circulating lipids (10) and FFAs (35).”
From Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus (2001) · cites this paper as [34]
In the citing paper
“It reduces reactive oxygen species (ROS) by inhibiting mitochondrial respiration [100] and decreases advanced glycosylation end product (AGE) indirectly through reduction of hyperglycemia and directly through an insulin-dependent mechanism [101].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [100]
In the citing paper
“Metformin has been proposed to cause a mild and transient inhibition of mitochondrial complex I which decreases ATP levels and activates AMPK-dependent catabolic pathways [100], increasing lipolysis and ß-oxidation in white adipose tissue [102] and reducing neoglucogenesis [2].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [100]
In the citing paper
“It can upregulate uncoupled proteins 2 (UCP2) in adipose tissue [102] and can also cause an increase in reduced glutathione [100].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [100]
Citations
Cites
Metabolic effects of metformin in non-insulin-dependent diabetes mellitus
Stumvoll, M., Nurjhan, N., Perriello, G., Dailey, G., & Gerich, J. E. (1995) · New England Journal of Medicine · doi:10.1056/nejm199508313330903 · Cited by 1,148
The physiological role of zinc as an antioxidant
Bray, T. Μ., & Bettger, W. J. (1990) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(90)90076-u · Cited by 896
Arnaud, J., Fortis, I., Blachier, S., Kia, D., & Favier, A. E. (1991) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/0378-4347(91)80476-s · Cited by 328
Biological origin of free radicals, and mechanisms of antioxidant protection
Gutteridge, J. M. C. (1994) · Chemico-Biological Interactions · doi:10.1016/0009-2797(94)90033-7 · Cited by 317
Oxidative stress and insulin action: is there a relationship?
Paolisso, G., & Giugliano, D. (1996) · Diabetologia · doi:10.1007/bf00418354 · Cited by 291
Cellular Mechanism of Action of Metformin
Klip, A., & Leiter, L. A. (1990) · Diabetes Care · doi:10.2337/diacare.13.6.696 · Cited by 239
Perriello, G., Misericordia, P., Volpi, E., Santucci, A., Santucci, C., Ferrannini, E., Ventura, M. M., Santeusanio, F., Brunetti, P., & Bolli, G. B. (1994) · Diabetes · doi:10.2337/diab.43.7.920 · Cited by 227
Mechanism of insulin resistance in fructose-fed rats
Tobey, T. A., Mondon, C. E., Zavaroni, I., & Reaven, G. M. (1982) · Metabolism · doi:10.1016/0026-0495(82)90100-7 · Cited by 191
Faure, P., Rossini, E., Lafond, J. L., Richard, M. J., Favier, A. E., & Halimi, S. (1997) · Journal of Nutrition · doi:10.1093/jn/127.1.103 · Cited by 171
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
Cited by
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Kinaan, M., Ding, H., & Triggle, C. R. (2015) · Medical Principles and Practice · doi:10.1159/000381643 · Cited by 1,515
Metformin: An Old But Still the Best Treatment for Type 2 Diabetes
Rojas, L. B. A., & Gomes, M. B. (2013) · Diabetology & Metabolic Syndrome · doi:10.1186/1758-5996-5-6 · Cited by 567
Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus
Mather, K. J., Verma, S., & Anderson, T. J. (2001) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(01)01129-9 · Cited by 513
Glucose and reactive oxygen species
Bonnefont‐Rousselot, D. (2002) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200209000-00016 · Cited by 464
Consequences of the diabetic status on the oxidant/antioxidant balance.
Bonnefont‐Rousselot, D., Bastard, J., Jaudon, M. C., & Delattre, J. (2000) · PubMed · Cited by 424
Metadata
- Authors
- Faure, P., Rossini, E., Wiernsperger, N., Richard, M. J., Favier, A., & Halimi, S.
- Affiliations
- Groupe de Recherché sur les Pathologies Oxydatives, UFR de Pharmacie, La Tronche, France. patrice.faure@ujf-grenoble.fr
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1999-02-01
- Volume
- 48
- Issue
- 2
- Pages
- 353-357
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2150046218
- Cited by
- 166
- References
- 14
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 11 · 2015: 10 · 2014: 5 · 2013: 10 · 2012: 6
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- metformin, insulin sensitivity, insulin resistance, high-fructose diet, oxidative stress, antioxidant defense, superoxide dismutase, glutathione, free radicals, glucose clamp
- MeSH terms
- Animals, Dietary Carbohydrates, Fructose, Hypoglycemic Agents, Insulin, Lipid Peroxides, Male, Metformin, Oxidoreductases, Free Radical Scavengers, Rats, Wistar, Rats
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