α-Lipoic Acid Prevents the Increase in Atherosclerosis Induced by Diabetes in Apolipoprotein E–Deficient Mice Fed High-Fat/Low-Cholesterol Diet
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Considerable evidence indicates that hyperglycemia increases oxidative stress and contributes to the increased incidence of atherosclerosis and cardiovascular complications in diabetic patients. To examine the effect of α-lipoic acid, a potent natural antioxidant, on atherosclerosis in diabetic mice, 3-month-old apolipoprotein (apo) E-deficient (apoE−/−) mice were made diabetic by administering streptozotocin (STZ). At 4 weeks after starting the STZ administration, a high-fat diet with or without α-lipoic acid (1.65 g/kg) was given to the mice and to nondiabetic apoE−/− controls. At 20 weeks, markers of oxidative stress were significantly lower in both the diabetic apoE−/− mice and their nondiabetic apoE−/− controls with α-lipoic acid supplement than in those without it. Remarkably, α-lipoic acid completely prevented the increase in plasma total cholesterol, atherosclerotic lesions, and the general deterioration of health caused by diabetes. These protective effects of α-lipoic acid were accompanied by a reduction of plasma glucose and an accelerated recovery of insulin-producing cells in the pancreas, suggesting that part of its effects are attributable to protecting pancreatic β-cells from damage. Our results suggest that dietary α-lipoic acid is a promising protective agent for reducing cardiovascular complications of diabetes.
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Traditional exogenous antioxidants and compounds with antioxidant properties reduce oxidative stress but have limited cellular uptake and do not accumulate where needed.
“Traditional exogenous antioxidants (for example, vitamins E, C and D), as well as chemical compounds with described antioxidants properties (for example, coenzyme Q, α-lipoic acid and N-acetylcysteine), have been used to reduce oxidative stress279,280, but their cellular uptake is limited and they do not accumulate where needed281.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [280]
α-Lipoic acid improved β-cell function in apolipoprotein E-deficient mice given STZ.
“and improved β-cell function in apolipoprotein E–deficient mice given STZ (339).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [339]
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- Authors
- Yi, X., & Maeda, N.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2006-08-01
- Volume
- 55
- Issue
- 8
- Pages
- 2238-2244
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2103996548
- Cited by
- 117
- References
- 49
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 7 · 2021: 1 · 2020: 7 · 2019: 6 · 2018: 5 · 2017: 10 · 2016: 3 · 2015: 1 · 2014: 7 · 2013: 4 · 2012: 13
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DK-34987)
- National Heart, Lung, and Blood Institute (U01HL087946, U01HL070523, HL 42630, HL-70523, R01HL077145)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 34987, P30DK034987)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Keywords
- alpha-lipoic acid, atherosclerosis, ApoE-deficient mice, streptozotocin-induced diabetes, oxidative stress, hyperglycemia, serum cholesterol, atherosclerotic plaque, beta-cell recovery, antioxidants, cardiovascular complications of diabetes
- MeSH terms
- Animals, Antioxidants, Apolipoproteins E, Blood Glucose, Cholesterol, Dietary, Diabetes Mellitus, Experimental, Diet, Dietary Fats, Erythrocytes, Glutathione, Immunohistochemistry, Lipids, Thioctic Acid, Male, Mice, Inbred C57BL, Biomarkers, Thiobarbituric Acid Reactive Substances, Mice, Knockout, Oxidative Stress, Aryldialkylphosphatase, Atherosclerosis, Mice
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