Effect of Paraquat-Induced Oxidative Stress on Insulin Regulation of Insulin-Like Growth Factor-Binding Protein-1 Gene Expression

Kimura, Kumi; Ozawa, Tetsuya; Tawara, Satoshi; Igarashi, Kiharu; Cho, Yoshitake; Shibata, Norihiro; Hakuno, Fumihiko; Takahashi, Shin‐Ichiro; Takenaka, Asako

doi:10.3164/jcbn.09-97

Cited by 10 publications

(10 citation statements)

References 55 publications

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“…6). The transcription of Igfbp-1 in liver is repressed by insulin, and this repression is impaired by oxidative stress due to the interruption of insulin-dependent phosphorylation of mammalian target of rapamycin (Kimura et al , 2010). Therefore, the increased mRNA of Igfbp-1 in Nrf2-null mice could be due to the more oxidative cellular environment in their hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

Zhang

Liu

et al. 2012

Toxicology and Applied Pharmacology

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Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling.

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Section: Discussionmentioning

confidence: 99%

Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

Zhang

Liu

et al. 2012

Toxicology and Applied Pharmacology

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“…In addition, Igfbp1 significantly increased in the DEN-I3C group and decreased in the DEN-I3C-NAC group compared to the DENalone group. Kimura et al (2010) reported that Paraquatinduced oxidative stress increased Igfbp1, while addition of NAC treatment decreased Igfbp1 in rat hepatocytes. Therefore, fluctuations of Glrx1and Igfbp1 in the present study indicate that oxidative stress is enhanced by the I3C treatment, but is directly depressed by NAC treatment.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant N-acetyl-L-cysteine (NAC) supplementation reduces reactive oxygen species (ROS)-mediated hepatocellular tumor promotion of indole-3-carbinol (I3C) in rats

et al. 2011

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-Indole-3-carbinol (I3C) has a liver tumor promoting activity in rats, and is also known as a cytochrome p450 1A (CYP1A) inducer. The generation of reactive oxygen species (ROS) resulting from CYP1A induction due to I3C, is probably involved in the tumor promotion. To clarify whether ROS generation contributes to I3C's induction of hepatocellular altered foci, partially hepatectomized rats were fed a diet containing 0.5% of I3C for 8 weeks with or without 0.3% N-acetyl-L-cysteine (NAC), an antioxidant, in their drinking water after N-diethylnitrosamine (DEN) initiation. Immunohistochemical analysis showed that the glutathione-S-transferase placental form (GST-P) positive foci promoted by I3C were suppressed by the administration of NAC. The mRNAs of members of the phase II nuclear factor, erythroid derived 2, like 2 (Nrf2) gene batteries, whose promoter region is called as antioxidant response element (ARE), were down-regulated in the DEN-I3C-NAC group compared to the DEN-I3C group, but Cyp1a1 was not suppressed in the DEN-I3C-NAC group compared to the DEN-I3C group. There was no marked difference in production of microsomal ROS and genomic 8-hydroxy-2′-deoxygunosine (8-OHdG) as an oxidative DNA marker between the DEN-I3C-NAC and DEN-I3C groups, while mapkapk3 and Myc were decreased by the NAC treatment. These results indicate that oxidative stress plays an important role for I3C's tumor promotion, and NAC suppresses induction of hepatocellular altered foci with suppressed cytoplasmic oxidative stress.

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“…In this stage, nitric oxide NObinds with O2resulting in peroxynitrite ONOO - (14). The state of oxidative stress plays a role in the creation of insulin resistance (15) which can be explained as a result of the inhibitory action of ROS on the gene of insulin receptors in addition to the destructive action of ROS on molecules that promotes insulin secretion (16). Also there will be an impeding in glucose entry to the cells (17).…”

Section: Discussionmentioning

confidence: 99%

Effect of Dexamethasone on Liver Function in Male Rats Exposed to Paraquat

Kakel¹

2012

Bas.J.Vet.Res.

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This study was conducted to evaluate the usage of dexamethasone (Dx) in the treatment of liver function tests in experimental paraquat (PQ)-induced oxidative stress in male albino rats. Three groups of rats were subjected to this trial, control, PQ group (50 mg/ kg orally) and PQ with Dx (50 mg/ kg orally, 4 mg/ kg ip. Respectively)daily throughout the 15 days. Results revealed that treatment with PQ caused a mortality rate in a ratio of 30%,significantly increased (p≤0.05) of glucose, cholesterol, bilirubin concentrations and alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and amylase activities but the concentrations of both triglycerides and serum proteins were reduced compared with control whereas the treatment of PQ-treated rats with Dx decreased mortality rate (30%) and corrected the activity of serum transaminases, alkaline phosphatase enzymes whereas Dx treatment induced an elevation in amylase activityin addition to the elevation of concentrations of total cholesterol, total protein and albumin in comparison with values of PQ-treated rats, Dx did not affect the concentration of glucose. In conclusion, the treatment of PQ-induced toxicity with Dx in rats was efficient in correction of most liver function tests.

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Effect of Paraquat-Induced Oxidative Stress on Insulin Regulation of Insulin-Like Growth Factor-Binding Protein-1 Gene Expression

Cited by 10 publications

References 55 publications

Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

Antioxidant N-acetyl-L-cysteine (NAC) supplementation reduces reactive oxygen species (ROS)-mediated hepatocellular tumor promotion of indole-3-carbinol (I3C) in rats

Effect of Dexamethasone on Liver Function in Male Rats Exposed to Paraquat

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