Insulinoma cells in culture show pronounced sensitivity to alloxan-induced oxidative stress

Zhang, H.; Öllinger, Karin; Brunk, Ulf T.

doi:10.1007/bf00401832

Cited by 59 publications

(32 citation statements)

References 32 publications

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“…In cells, SOD catalyzes the conversion of O 2 -to H 2 O 2 , and H 2 O 2 is further reduced to H 2 O by the activity of CAT or GSH-px. Pancreatic β cells have been reported to contain low levels of endogenous antioxidant enzymes, particularly GSH-px and CAT (27). In the present study, SIN-1-treated HIT-T15 cells were shown to have decreased GSH-px and CAT activities, which may be due to the increased oxidative damage induced by SIN-1.…”

Section: Discussionsupporting

confidence: 42%

Protective effects of Lagerstroemia speciosa on 3-morpholinosydnonimine (SIN-1)-induced oxidative stress in HIT-T15 pancreatic β cells

Song

Zhao

Wang

et al. 2013

Molecular Medicine Reports

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Abstract. Reactive oxygen species (ROS)-induced pancreatic β cell death affects insulin secretion and is important in the pathogenesis of diabetes. Lagerstroemia speciosa, a traditional folk medicine, has been used for t he prevention and treatment of diabetes. However, whether Lagerstroemia speciosa has a cytoprotective effect on pancreatic β cells remains to be elucidated. The present study aimed to investigate the cytoprotective effects of hot water extracts from Lagerstroemia speciosa leaves (LWE) on 3-morpholinosydnonimine (SIN-1)-induced oxidative damage in Syrian hamster pancreatic insulinoma HIT-T15 cells. The HIT-T15 cells were first treated with SIN-1 (50 µM) for 24 h and then co-incubated with LWE for 48 h. SIN-1 significantly decreased HIT-T15 cell viability (P<0.05); however, LWE did not exert a significant cytotoxic effect and increased the viability of HIT-T15 cells in a dose-dependent manner. To further investigate the protective effects of LWE on SIN-1-induced oxidative stress in HIT-T15 cells, the cellular levels of ROS, lipid peroxidation and endogenous antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px), were determined. LWE decreased the intracellular levels of ROS and lipid peroxidation, and increased the activities of antioxidant enzymes. These results suggest that LWE has a cytoprotective effect against SIN-1-induced oxidative stress in HIT-T15 cells through the inhibition of lipid peroxidation, a decrease in ROS levels and an increase in antioxidant enzyme activity. In addition, LWE increased insulin secretion in SIN-1-treated HIT-T15 cells. Our results suggested that LWE were effective in the treatment of diabetes. Further studies are required to study the anti-diabetic molecular mechanism in a cell model.

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Section: Discussionsupporting

confidence: 42%

Protective effects of Lagerstroemia speciosa on 3-morpholinosydnonimine (SIN-1)-induced oxidative stress in HIT-T15 pancreatic β cells

Song

Zhao

Wang

et al. 2013

Molecular Medicine Reports

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“…1.5 min. at neutral pH and 37°C in physiological solutions (Zhang et al 1995), it is reported to generate both extra-and intra-cellular ROS (free radicals), which are responsible for its toxic effect. ALX is extracellularly reduced to dialuric acid through interaction with any available cysteine, GSH or sulfhydryl group at the extracellular plasma membrane sites, followed by the auto-oxidation of dialuric acid back to ALX resulting in redox-cycling.…”

Section: Discussionmentioning

confidence: 99%

“…ALX is extracellularly reduced to dialuric acid through interaction with any available cysteine, GSH or sulfhydryl group at the extracellular plasma membrane sites, followed by the auto-oxidation of dialuric acid back to ALX resulting in redox-cycling. This is accompanied by superoxide anion radicals (O 2 Á) and hydrogen peroxide (H 2 O 2 ), of which the latter can diffuse into the intracellular compartment (Winterbourn and Munday 1989;Lenzen and Munday 1991;Zhang et al 1995;Szkudelski 2001). Other studies have suggested that the basis for the toxicity of ALX to pancreatic b-cells is that it is taken up into the cells via the Glut 2 glucose transporter, where it is reduced to dialuric acid by intracellular cysteine and/or GSH (Elsner et al 2002(Elsner et al , 2006.…”

Section: Discussionmentioning

confidence: 99%

Suppressive effects of electrolyzed reduced water on alloxan-induced apoptosis and type 1 diabetes mellitus

Hamasaki

Nakamichi³

et al. 2010

Cytotechnology

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Electrolyzed reduced water, which is capable of scavenging reactive oxygen species, is attracting recent attention because it has shown improved efficacy against several types of diseases including diabetes mellitus. Alloxan produces reactive oxygen species and causes type 1 diabetes mellitus in experimental animals by irreversible oxidative damage to insulin-producing b-cells. Here, we showed that electrolyzed reduced water prevented alloxaninduced DNA fragmentation and the production of cells in sub-G1 phase in HIT-T15 pancreatic b-cells. Blood glucose levels in alloxan-induced type 1 diabetes model mice were also significantly suppressed by feeding the mice with electrolyzed reduced water. These results suggest that electrolyzed reduced water can prevent apoptosis of pancreatic b-cells and the development of symptoms in type 1 diabetes model mice by alleviating the alloxan-derived generation of reactive oxygen species.Keywords Electrolyzed reduced water Á Alloxan Á Type 1 diabetes mellitus Á Reactive oxygen species Á HIT-T15 cells

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“…Because islet cells and insulinoma cells possess only low concentrations of oxygen free-radical scavenging enzymes (Oberley, 1988), their cellular function is easily damaged (Burkart et al, 1992;Mandrup-Poulsen et al, 1990;Zhang et al, 1995). The highly reactive hydroxyl radical ( • OH) is generated via the iron mediated Fenton reaction (Cross et al, 1987) from the superoxide anion radical ( • O2) and hydrogen peroxide (H2O2), which is known to be produced in pancreatic islets by STZ or ALX (Takasu et al, 1991;Wilson et al, 1984).…”

mentioning

confidence: 99%

Diverse Effects of Hydrogen Peroxide on Cytosolic Ca2+ Homeostasis in Rat Pancreatic .BETA.-cells.

Nakazaki

Kakei

Yaekura

et al. 2000

Cell Struct. Funct.

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ABSTRACT. Oxygen-free radicals are thought to be a major cause of b-cell dysfunction in diabetic animals induced by alloxan or streptozotocin. We evaluated the effect of H2O2 on cytosolic Ca 2+ concentration ([Ca 2+ ]i) and the activity of ATP-sensitive potassium (K + ATP) channels in isolated rat pancreatic b-cells using microfluorometry and patch clamp techniques. Exposure to 0.1 mM H2O2 in the presence of 2.8 mM glucose increased [Ca 2+ ]i from 114.3±15.4 nM to 531.1±71.9 nM (n=6) and also increased frequency of K + ATP channel openings. The intensity of NAD(P)H autofluorescence was conversely reduced, suggesting that H2O2 inhibited the cellular metabolism. These three types of cellular parameters were reversed to the control level on washout of H2O2, followed by a transient increase in [Ca 2+ ]i, the transient inhibition of K + ATP channels associated with action currents and increase of the NAD(P)H intensity with an overshoot. In the absence of external Ca 2+ , 0.1 mM H2O2 increased [Ca 2+ ]i from 88.8±7.2 nM to 134.6±8.3 nM. Magnitude of [Ca 2+ ]i increase induced by 0.1 mM H2O2 was decreased after treatment of cells with 0.5 mM thapsigargin, an inhibitor of endoplasmic reticulum Ca 2+ pump (45.8±4.9 nM vs 15.0±4.8 nM). Small increase in [Ca 2+ ]i in response to an increase of external Ca 2+ from zero to 2 mM was further facilitated by 0.1 mM H2O2 (330.5±122.7 nM). We concluded that H2O2 not only activates K + ATP channels in association with metabolic inhibition, but also increases partly the Ca 2+ permeability of the thapsigargin-sensitive intracellular stores and of the plasma membrane in pancreatic b-cells.

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Insulinoma cells in culture show pronounced sensitivity to alloxan-induced oxidative stress

Cited by 59 publications

References 32 publications

Protective effects of Lagerstroemia speciosa on 3-morpholinosydnonimine (SIN-1)-induced oxidative stress in HIT-T15 pancreatic β cells

Protective effects of Lagerstroemia speciosa on 3-morpholinosydnonimine (SIN-1)-induced oxidative stress in HIT-T15 pancreatic β cells

Suppressive effects of electrolyzed reduced water on alloxan-induced apoptosis and type 1 diabetes mellitus

Diverse Effects of Hydrogen Peroxide on Cytosolic Ca2+ Homeostasis in Rat Pancreatic .BETA.-cells.

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