Relationships among pancreatic beta cell function, the Nrf2 pathway, and IRS2: a cross-sectional study

Liu, Yiying; Zeng, Yue; Miao, Ying; Cheng, Xiaoling; Deng, Sijie; Hao, Xinlin; Jiang, Yuefei; Wan, Qin

doi:10.1080/00325481.2020.1797311

Cited by 6 publications

(7 citation statements)

References 20 publications

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“…Furthermore, Nrf2 activation decreased the expression of inflammatory mediators and protected human β cells against oxidative stress [127]. Interestingly, a study that evaluated tumor necrosis factor-alpha (TNF-α), Nrf2, and HO-1 levels in normal glucose tolerance, patients with pre-DM, and T2DM found that TNF-α increased Nrf2 and HO-1 decreased as patients became more diabetic, suggesting that, along with aggravation of oxidative stress and inflammatory response, Nrf2 activation and HO-1 expression were both inhibited [128]. One possible explanation of the decline in Nrf2 and HO-1 activity is through the downregulation of PI3K/AKT pathway under conditions of oxidative stress.…”

Section: Antioxidant Properties Of β Cellsmentioning

confidence: 99%

The Role of Oxidative Stress in Pancreatic β Cell Dysfunction in Diabetes

Eguchi

Vaziri

Dafoe

et al. 2021

IJMS

171

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Diabetes is a chronic metabolic disorder characterized by inappropriately elevated glucose levels as a result of impaired pancreatic β cell function and insulin resistance. Extensive studies have been conducted to elucidate the mechanism involved in the development of β cell failure and death under diabetic conditions such as hyperglycemia, hyperlipidemia, and inflammation. Of the plethora of proposed mechanisms, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and oxidative stress have been shown to play a central role in promoting β cell dysfunction. It has become more evident in recent years that these 3 factors are closely interrelated and importantly aggravate each other. Oxidative stress in particular is of great interest to β cell health and survival as it has been shown that β cells exhibit lower antioxidative capacity. Therefore, this review will focus on discussing factors that contribute to the development of oxidative stress in pancreatic β cells and explore the downstream effects of oxidative stress on β cell function and health. Furthermore, antioxidative capacity of β cells to counteract these effects will be discussed along with new approaches focused on preserving β cells under oxidative conditions.

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Section: Antioxidant Properties Of β Cellsmentioning

confidence: 99%

The Role of Oxidative Stress in Pancreatic β Cell Dysfunction in Diabetes

Eguchi

Vaziri

Dafoe

et al. 2021

IJMS

171

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“…Given that oxidative stress exacerbates T2DM, antioxidant therapy has gained more attention [ 41 ]. It has been shown that the Nrf2 pathway is inhibited in response to oxidative stress stimuli and impaired islet function is exacerbated, possibly mediated by PI3K/AKT [ 42 ]. In addition, natural active components in plants, such as sulforaphane, can effectively modulate Nrf2 [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

The Positive Effect of 6-Gingerol on High-Fat Diet and Streptozotocin-Induced Prediabetic Mice: Potential Pathways and Underlying Mechanisms

et al. 2023

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The purposes of the present work are to assess how 6-gingerol (6G) positively influences serum glucose regulation in mice with prediabetes triggered by streptozotocin (STZ) plus a high-fat diet (HFD) and to clarify its underlying mechanisms. An analysis of prediabetic symptoms and biochemical characteristics found that 6G intervention was significantly associated with reduced fasting glucose levels, alleviated insulin resistance, better glucose tolerance, hepatic and pancreatic impairment, and dyslipidemia. For the recognition of the target gut microbiota and the pathways linked to 6G’s hypoglycemic function, a combination of hepatic RNA and 16S rRNA sequencing was employed. Specifically, 6G significantly improved the dysbiosis of the gut microbiota and elevated the relative abundances of Alistipes, Alloprevotella, and Ruminococcus_1. Furthermore, 6G supplementation inhibited gluconeogenesis and stimulated glycolysis by activating the PI3K/AKT axis, which also repressed the oxidative stress through Nrf2/Keap1-axis initiation. In addition, Spearman’s correlation analyses reveal a complex interdependency set among the gut microbiota, metabolic variables, and signaling axes. Taken together, the hypoglycemic effect of 6G is partially mediated by altered gut microbiota, as well as by activated Nrf2/Keap1 and PI3K/AKT axes. Thus, 6G may be used as a candidate dietary supplement for relieving prediabetes.

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“…In conjunction with the altered redox balance, the protein levels of Nrf2 and its downstream HO-1 were significantly reduced in LCT group. Nrf2 is the master regulator of the antioxidant response element (ARE)-driven gene expression, which encodes phase II detoxifying enzymes like HO-1 and NADPH quinone oxidoreductase 1 (NQO-1); the antioxidant enzymes like CAT, SOD, and GPx; and the non-enzymatic antioxidants like GSH 44 . In pancreas, Nrf2 protects β-cells against diabetic stresses via amelioration of oxidative stress, maintenance of β-cells mass, preservation of insulin content and secretion, and regulation of mitochondrial function and biogenesis 45 .…”

Section: Discussionmentioning

confidence: 99%

Lambda-cyhalothrin-induced pancreatic toxicity in adult albino rats

Sakr

Rashad

2023

Sci Rep

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Lambda-cyhalothrin (LCT) is one of the most frequently utilized pyrethroids. This study aimed to explore the toxic effects of subacute exposure to LCT on the pancreas and the hepatic glucose metabolism in adult male albino rats. 20 rats were equally grouped into; Control group and LCT group. The latter received LCT (61.2 mg/kg b.wt.), orally on a daily basis for 28 days. At the end of experiment, blood samples were collected for the determination of serum glucose and insulin levels. Pancreases were harvested and levels of malondialdehyde (MDA); catalase (CAT); superoxide dismutase (SOD); reduced glutathione (GSH); tumor necrosis factor-α (TNF-α); interleukin-6 (IL-6); nuclear factor erythroid 2–related factor 2 (Nrf2); heme oxygenase 1 (HO-1); and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were assessed. Also, liver samples were analyzed for the activity of glucose metabolism enzymes, glycogen content, and pyruvate and lactate concentrations. Histopathological and immunohistochemical examinations of pancreatic tissues were undertaken as well. Results revealed hyperglycemia, hypoinsulinemia, increased MDA, TNF-α, IL-6, and NF-κB levels, in association with reduced CAT, SOD, GSH, Nrf2, and HO-1 levels in LCT group. Liver analyses demonstrated a clear disturbance in the hepatic enzymes of glucose metabolism, diminished glycogen content, decreased pyruvate, and increased lactate concentrations. Besides, pancreatic islets displayed degenerative changes and β-cells loss. Immunohistochemistry revealed diminished area percentage (%) of insulin and Nrf2 and increased TNF-α immunoreaction. In conclusion, subacute exposure to LCT induces pancreatic toxicity, mostly via oxidative and inflammatory mechanisms, and dysregulates hepatic glucose metabolism in albino rats.

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Relationships among pancreatic beta cell function, the Nrf2 pathway, and IRS2: a cross-sectional study

Cited by 6 publications

References 20 publications

The Role of Oxidative Stress in Pancreatic β Cell Dysfunction in Diabetes

The Role of Oxidative Stress in Pancreatic β Cell Dysfunction in Diabetes

The Positive Effect of 6-Gingerol on High-Fat Diet and Streptozotocin-Induced Prediabetic Mice: Potential Pathways and Underlying Mechanisms

Lambda-cyhalothrin-induced pancreatic toxicity in adult albino rats

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