Antioxidant α‐tocopherol ameliorates glycemic control of GK rats, a model of type 2 diabetes

Ihara, Yu; Yamada, Yoshio; Toyokuni, Shinya; Miyawaki, Kazumasa; Ban, Nobuhiro; Adachi, Tomohiko; Kuroe, Akira; Iwakura, Toshio; Kubota, Akira; Hayashi, Hiroshi; Seino, Yutaka

doi:10.1016/s0014-5793(00)01489-7

Cited by 112 publications

(72 citation statements)

References 33 publications

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“…The addition of antioxidants reversed the negative effects of high glucose on extracellular matrix proteins and cell growth (34,37,38). The strongest previously published evidence supporting the hypothesis that glucose toxicity in ␤ cells is mediated by ROS is indirect, i.e., demonstrations in vitro and in vivo of protective effects of antioxidants against the deterioration of insulin gene expression and ␤ cell function associated with supraphysiologic glucose levels (19,20,24). The current studies provide direct evidence that glucose and ribose increase intracellular peroxide levels in isolated human and rat pancreatic islets, and that the intrinsically low levels of ␤ cell GPx activity (25,26) predispose them to ROS-induced damage.…”

Section: Discussionmentioning

confidence: 88%

“…Decreased PDX-1 leads to diminished ␤ cell insulin content and defective glucose-induced insulin secretion. The toxic effects of elevated glucose and ribose can be prevented by antioxidants in a ␤ cell line (20) and animal models of type 2 diabetes (19,20,24). The beneficial effects of antioxidants may be related to the low levels of antioxidant enzyme activity that are characteristic of islets (25, 26), which render them particularly susceptible to the oxidative effects of ROS.…”

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confidence: 99%

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A role for glutathione peroxidase in protecting pancreatic β cells against oxidative stress in a model of glucose toxicity

Tanaka

Tran

Harmon

et al. 2002

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

296

264

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Antioxidant drugs have been reported to protect pancreatic islets from the adverse effects of chronic exposure to supraphysiological glucose concentrations. However, glucose has not been shown to increase intracellular oxidant load in islets, nor have the effects of increasing or inhibiting glutathione peroxidase (GPx) activity on islet resistance to sugar-induced oxidant stress been studied. We observed that high glucose concentrations increased intracellular peroxide levels in human islets and the pancreatic ␤ cell line, HIT-T15. Inhibition of ␥-glutamylcysteine synthetase (␥GCS) by buthionine sulfoximine augmented the increase in islet peroxide and decrease in insulin mRNA levels, content, and secretion in islets and HIT-T15 cells induced by ribose. Adenoviral overexpression of GPx increased GPx activity and protected islets against adverse effects of ribose. These results demonstrate that glucose and ribose increase islet peroxide accumulation and that the adverse consequences of ribose-induced oxidative stress on insulin mRNA, content, and secretion can be augmented by a glutathione synthesis inhibitor and prevented by increasing islet GPx activity. These observations support the hypothesis that oxidative stress is one mechanism for glucose toxicity in pancreatic islets. T ype 2 diabetes mellitus is polygenic in origin and usually begins in adulthood, although specific genes for subtypes of this disease that occur earlier in life, referred to collectively as maturity-onset diabetes of the young (MODY), have been identified (1). The onset of type 2 diabetes is insidious, thus hyperglycemia develops gradually and often goes untreated for years until symptoms become clinically obvious. Consequent chronic exposure of tissues to supraphysiologic levels of blood glucose can lead to adverse intracellular outcomes, a process known as glucose toxicity (2-5). Possible mechanisms of action for glucose toxicity include the formation of advanced glycosylation end products and glucosamine, increased protein kinase C activity with c-myc induction, autooxidation of glucose, and increased levels of reactive glycolytic intermediates such as glyceraldehyde-3-phosphate or dihydroxyacetone phosphate (6 -13). All these processes usually are accompanied by the formation of reactive oxygen species (ROS), setting up the potential for oxidative stress. Many weeks of exposure to high concentrations of glucose are necessary before glucotoxic effects are expressed by islet ␤ cells in vitro and in vivo (14 -20). Because isolated islets do not reliably survive in culture greater than 2 weeks, the use of short-term exposure to ribose, a sugar that generates ROS more potently than glucose, has become an accepted model for studying islet glucose toxicity (21,22). The use of ribose as a prooxidant sugar is especially valuable in adenoviral overexpression systems, because the overexpression effect is short-lived, lasting only days.In the pancreatic ␤ cell, glucose and ribose toxicity cause decreased insulin mRNA levels (14-22), one mechanism ...

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Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

A role for glutathione peroxidase in protecting pancreatic β cells against oxidative stress in a model of glucose toxicity

Tanaka

Tran

Harmon

et al. 2002

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

296

264

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“…Despite this adaptation, prolonged exposure to elevated glucose levels causes not only impaired insulin responsiveness, but also beta cell loss, due to ROS (30) arising from mitochondria (31,32) and nonenzymatic glycation (33)(34)(35). This damage can be substantially prevented by the in vivo administration of antioxidants (36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Absence of a reductase, NCB5OR, causes insulin-deficient diabetes

Xie

Zhu

Larade

et al. 2004

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

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NCB5OR is a highly conserved NAD(P)H reductase that contains a cytochrome b5-like domain at the N terminus and a cytochrome b5 reductase-like domain at the C terminus. The enzyme is located in the endoplasmic reticulum (ER) and is widely expressed in organs and tissues. Targeted inactivation of this gene in mice has no impact on embryonic or fetal viability. At 4 weeks of age, Ncb5or؊͞؊ mice have normal blood glucose levels but impaired glucose tolerance. Isolated Ncb5or؊͞؊ islets have markedly impaired glucose-or arginine-stimulated insulin secretion. By 7 weeks of age, these mice develop severe hyperglycemia with markedly decreased serum insulin levels and nearly normal insulin tolerance. As the animals age, there is a progressive loss of beta cells in pancreatic islets, but there is no loss of alpha, delta, or PP cells. Electron microscopy reveals degranulation of beta cells and hypertrophic and hyperplastic mitochondria, some of which contain electron dense inclusions. Four-week-old Ncb5or؊͞؊ mice have enhanced sensitivity to the diabetogenic agent streptozotocin. NCB5OR appears to play a critical role in protecting pancreatic beta cells against oxidant stress.

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“…Vitamin E has been shown to controls hyperglycemia and lowering the HbA1c by inhibiting the sequence of oxidative stress in diabetic rats [15]. The mechanism by which antioxidants reduced the glucose levels not yet clear, but the plasma glucose level decreased by increasing the glucose metabolism in peripheral tissues [16].…”

Section: Vitamin Ementioning

confidence: 99%

A Review on Role of Antioxidants in Diabetes

Rajendiran

Packirisamy

Giribabu³

2018

Asian J Pharm Clin Res

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Diabetes mellitus is a chronic metabolic disease. Oxidative stress plays a major part in the pathogenesis of diabetes. Supplementation with antioxidants and the medicinal plants which possess antioxidants activity have been reported their hypoglycemic activity. The antioxidants are used to treat and reduce the complication of diabetes mellitus. The diet supplementations of antioxidants vitamins are beneficial in the treatment of diabetes. This review article was summarizing the role of antioxidants in diabetes mellitus.

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Antioxidant α‐tocopherol ameliorates glycemic control of GK rats, a model of type 2 diabetes

Cited by 112 publications

References 33 publications

A role for glutathione peroxidase in protecting pancreatic β cells against oxidative stress in a model of glucose toxicity

A role for glutathione peroxidase in protecting pancreatic β cells against oxidative stress in a model of glucose toxicity

Absence of a reductase, NCB5OR, causes insulin-deficient diabetes

A Review on Role of Antioxidants in Diabetes

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