Modification of chemically induced diabetes in rats by vitamin E. Supplementation minimizes and depletion enhances development of diabetes.

Slonim, Alfred E.; Surber, Melanie L.; Page, Doris; Sharp, Robert A.; Burr, Ian M.

doi:10.1172/jci110878

Cited by 75 publications

(20 citation statements)

References 21 publications

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“…Our results add strength to the hypothesis, supported by animal experiments, that a sufficient intake of antioxidants plays a role in type 2 diabetes prevention (27,28). The results corroborate findings in earlier prospective studies, suggesting an inverse association between serum levels of total vitamin E, ␣-tocopherol, and incidence of type 2 diabetes (4,6).…”

Section: Methodssupporting

confidence: 90%

Dietary Antioxidant Intake and Risk of Type 2 Diabetes

et al. 2004

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OBJECTIVE -The intake of antioxidants was studied for its ability to predict type 2 diabetes.RESEARCH DESIGN AND METHODS -A cohort of 2,285 men and 2,019 women 40 -69 years of age and free of diabetes at baseline (1967)(1968)(1969)(1970)(1971)(1972) was studied. Food consumption during the previous year was estimated using a dietary history interview. The intake of vitamin C, four tocopherols, four tocotrienols, and six carotenoids was calculated. During a 23-year follow-up, a total of 164 male and 219 female incident cases occurred.RESULTS -Vitamin E intake was significantly associated with a reduced risk of type 2 diabetes. The relative risk (RR) of type 2 diabetes between the extreme quartiles of the intake was 0.69 (95% CI 0.51-0.94, P for trend ϭ 0.003). Intakes of ␣-tocopherol, ␥-tocopherol, ␦-tocopherol, and ␤-tocotrienol were inversely related to a risk of type 2 diabetes. Among single carotenoids, ␤-cryptoxanthin intake was significantly associated with a reduced risk of type 2 diabetes (RR 0.58, 95% CI 0.44 -0.78, P Ͻ 0.001). No association was evident between intake of vitamin C and type 2 diabetes risk.CONCLUSIONS -This study supports the hypothesis that development of type 2 diabetes may be reduced by the intake of antioxidants in the diet. Diabetes Care 27:362-366, 2004A lthough obesity and physical inactivity are known to be major risk factors for type 2 diabetes, recent evidence suggests that oxidative stress may contribute to the pathogenesis of type 2 diabetes by increasing insulin resistance or impairing insulin secretion (1). Dietary antioxidants have been hypothesized to have a protective effect against the development of diabetes by inhibiting peroxidation chain reactions (2). It seems plausible that a sufficient intake of antioxidants plays an important role in protection against type 2 diabetes. However, little epidemiological evidence is available on the role of dietary antioxidant intake in prevention of type 2 diabetes.In one prospective cohort study, vitamin C intake was significantly lower among incident cases of type 2 diabetes (3). In three prospective observational studies, serum ␣-tocopherol levels were associated with lower risk of type 1 or type 2 diabetes (4 -6). Serum ␤-carotene and ␣-tocopherol concentrations were nonsignificantly associated with a reduced risk in a cohort of Finns (7). In some case-control and cross-sectional studies, significantly lower serum levels of ␣-tocopherol, carotene, or vitamin C have been observed in individuals with diabetes than in control subjects (8 -13). In one American study, ␣-tocopherol concentrations were even higher in diabetic patients than in control subjects (14). Some prospective studies have shown that higher vegetable and fruit consumption may lower the risk of developing diabetes, suggesting that antioxidants in the diet may have a synergistic effect (3,15,16).Dietary vitamin E, four tocopherols, four tocotrienols, vitamin C, and six carotenoids were investigated for their ability to predict type 2 diabetes in a large prospective...

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Section: Methodssupporting

confidence: 90%

Dietary Antioxidant Intake and Risk of Type 2 Diabetes

et al. 2004

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“…Diabetes is a disease characterized by increased oxidative stress, as indicated by elevated concentrations of lipid peroxidation products in the plasma. 35) Slonim et al,8) demonstrated that administration of vitamin E to rats provided protection against the diabetogenic action of alloxan. Dillard et al,36) demonstrated that in vitamin E deficient rats alloxan induced an increase in levels of pentane and ethane in the expired breath and thiobarbituric acid reactive substances (TBARS) in plasma, liver and pancreas.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis and Mitochondrial Damage in INS-1 Cells Treated with Alloxan.

Sakurai

Katoh

Someno

et al. 2001

Biological & Pharmaceutical Bulletin

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A variety of mechanisms have been identified as responsible for the onset of diabetes mellitus. Alloxan shows a selective cytotoxicity on pancreatic b-cells and thus causes insulin-dependent (type I) diabetes mellitus. Although the mechanism of alloxan cytotoxicity is not yet clearly understood, several researchers 1,2) demonstrated that the diabetogenic action was initiated by the generation of reactive oxygen species (ROS). Alloxan is a mild oxidant and is easily reduced to alloxan radicals (A· Ϫ ) by GSH or ascorbic acid. 3) Our previous study 4) demonstrated that A· Ϫ can directly reduce O 2 and ferric ions to superoxide anion radical (O 2 · Ϫ ) and ferrous ions, respectively. The extreme and indiscriminate reactivity of ROS could easily explain the killing of b-cells by alloxan. In support of this hypothesis alloxan diabetes is prevented by HO · scavengers, 5-7) superoxide dismutase (SOD) 2) and vitamin E. 8) In addition, on the basis of in vivo and in vitro studies using rats and isolated islet cells, respectively, it was proposed that the process of alloxan toxicity involved the generation of HO · by which the DNA strands break of pancreatic islets is attacked to produce. 9-11) These findings indicate that DNA strand breaks are involved in the events of alloxan-diabetogenesis. However, the complex sequence of events that eventually leads to the DNA strand breaks and death of pancreatic b-cells in alloxan diabetes mellitus is not clear.Cell death might occur by one of two fundamental processes, necrosis or apoptosis. The biochemical hallmarks of apoptosis are the distribution of phosphatidylserine (PS) at the external surface of the plasma membrane (PS exposure) in the early stages, and the cleavage of chromosomal DNA into nucleosomal units, which appears to be the final blow in the cell death process. Recent studies have shown that different trigger such as IL-1b 12) and streptozotocin 13) can induce apoptosis in pancreatic b-cells. Although detailed studies indicate that alloxan can induce insulin-dependent diabetes mellitus, nothing is known about apoptotic action or the sequence of cellular events of alloxan on the b-cells.According to current understanding, mitochondrial damage seems to occur in the early phase of apoptosis and to participate in the control of apoptosis. 14,15) Release of cytochrome c and apoptosis induced factor from mitochondria into cytoplasm during mitochondrial permeability transition cause to active caspase family, leading to the completion of apoptosis. 15,16) Isolated liver mitochondria incubated with alloxan alters respiration, decreases in the concentration of adenine nucleotides, causes Ca 2ϩ release, and changes in the Dy, 17,18) indicating that alloxan directly induces the mitochondrial damage. However, the relationship between diabetes, apoptosis and mitochondrial damage has remained elusive.INS-1 cells were established by X-ray-induced rat transplantable insulinoma, and have retained the similar ability of glucose-stimulated insulin release of native b-cells. 19) INS-1 ...

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“…The alloxan toxicity has been attributed to its direct interactions with islet protein kinase (41) and to its well-known ability to generate highly reactive oxygen radicals (42,43). It is not yet clear whether the destructive effects of streptozotocin are also elicited by free radicals or whether they develop after alkylation of DNA bases (44)(45)(46)(47)(48)(49). Differences in protective conditions have often been considered as arguments in favor of a different action mechanism ofthe two diabetogenic compounds.…”

Section: Four Different Conditions Leading To B-cell Death In Vitromentioning

confidence: 99%

Pancreatic B cells possess defense mechanisms against cell-specific toxicity.

Pipeleers¹,

Winkel²

1986

Proc. Natl. Acad. Sci. U.S.A.

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Insulin-dependent diabetes develops when more than 90% of the insulin containing B cells are destroyed. The present study investigates whether the target B cells can counteract the damaging effects of cytotoxic substances. Purified islet cells were first exposed for 3-10 min to tbutylhydroperoxide, alloxan, streptozotocin, or B-cell surface antibodies plus complement, then cultured for 20 hr before the percent of dead cells was counted. t-Butylhydroperoxide destroyed all islet cell types whereas the three other agents exerted a dose-dependent toxicity upon islet B cells only. The survival of drug-and complement-treated cells varied with the culture conditions present between the initial cellular attack and the moment of cell death.

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Modification of chemically induced diabetes in rats by vitamin E. Supplementation minimizes and depletion enhances development of diabetes.

Cited by 75 publications

References 21 publications

Dietary Antioxidant Intake and Risk of Type 2 Diabetes

Dietary Antioxidant Intake and Risk of Type 2 Diabetes

Apoptosis and Mitochondrial Damage in INS-1 Cells Treated with Alloxan.

Pancreatic B cells possess defense mechanisms against cell-specific toxicity.

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