High glucose and hydrogen peroxide increase c-Myc and haeme-oxygenase 1 mRNA levels in rat pancreatic islets without activating NF?B

Elouil, Hajar; Cardozo, Alessandra K; Eizirik, Décio L.; Henquin, Jean Claude; Jonas, Jean‐Christophe

doi:10.1007/s00125-004-1664-4

Cited by 61 publications

(22 citation statements)

References 63 publications

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“…While these data have been widely accepted and clinical trials are underway to block IL-1 action in patients with T2DM, we and others have been unable to repeat these findings [191,192], (McKenzie et al unpublished).…”

Section: Glucosementioning

confidence: 63%

Beta cell apoptosis in diabetes

et al. 2009

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Apoptosis of beta cells is a feature of both type 1 and type 2 diabetes as well as loss of islets after transplantation. In type 1 diabetes, beta cells are destroyed by immunological mechanisms. In type 2 diabetes abnormal levels of metabolic factors contribute to beta cell failure and subsequent apoptosis. Loss of beta cells after islet transplantation is due to many factors including the stress associated with islet isolation, primary graft non-function and allogeneic graft rejection. Irrespective of the exact mediators, highly conserved intracellular pathways of apoptosis are triggered. This review will outline the molecular mediators of beta cell apoptosis and the intracellular pathways activated.

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Section: Glucosementioning

confidence: 63%

Beta cell apoptosis in diabetes

et al. 2009

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“…This does not seem to be the case, since acute (57) or overnight exposure to low concentrations of hydrogen peroxide does not increase rat islet NF-B activity and iNOS expression (56). Islet c-Myc and heme-oxygenase 1 expression are similarly induced by hydrogen peroxide and high glucose, and these effects are abrogated by the free radical scavenger N-acetyl-L-cysteine.…”

Section: Mechanisms Of ␤-Cell Death In Type 2 Diabetesmentioning

confidence: 95%

“…Islet c-Myc and heme-oxygenase 1 expression are similarly induced by hydrogen peroxide and high glucose, and these effects are abrogated by the free radical scavenger N-acetyl-L-cysteine. This suggests that ␤-cell glucotoxicity may, at least in part, result from an increase in ␤-cell oxidative stress and subsequent JNK activation that is NF-B independent (51,56). The main source of reactive oxygen species in the ␤-cell is probably the mitochondrial electron transport chain (58,59).…”

Section: Mechanisms Of ␤-Cell Death In Type 2 Diabetesmentioning

confidence: 99%

Mechanisms of Pancreatic β-Cell Death in Type 1 and Type 2 Diabetes

et al. 2005

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“…3). Of note, Myc is also an oxidative stress-responsive gene (Elouil et al 2005, Jonas et al 2009) that has been implicated in β-cell dedifferentiation (Jonas et al 2001, Laybutt et al 2002c, Pascal et al 2008, Robson et al 2011. On the other hand, it has been proposed that Myc expression is negatively regulated by PDX1 (Chen et al 2007).…”

Section: Downregulation Of Insulin Gene Expressionmentioning

confidence: 99%

“…Wistar rat islets (Bensellam et al 2009, Elouil et al 2005 Px rat islets (Jonas et al 2001, Jonas et al 1999 Gk rat islets (Lacraz et al 2010) mRNA…”

Section: Mycmentioning

confidence: 99%

Mechanisms of β-cell dedifferentiation in diabetes: recent findings and future research directions

Bensellam

Jonas

Laybutt

2018

Journal of Endocrinology

205

171

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Like all the cells of an organism, pancreatic β-cells originate from embryonic stem cells through a complex cellular process termed differentiation. Differentiation involves the coordinated and tightly controlled activation/repression of specific effectors and gene clusters in a time-dependent fashion thereby giving rise to particular morphological and functional cellular features. Interestingly, cellular differentiation is not a unidirectional process. Indeed, growing evidence suggests that under certain conditions, mature β-cells can lose, to various degrees, their differentiated phenotype and cellular identity and regress to a less differentiated or a precursor-like state. This concept is termed dedifferentiation and has been proposed, besides cell death, as a contributing factor to the loss of functional β-cell mass in diabetes. β-cell dedifferentiation involves: (1) the downregulation of β-cell-enriched genes, including key transcription factors, insulin, glucose metabolism genes, protein processing and secretory pathway genes; (2) the concomitant upregulation of genes suppressed or expressed at very low levels in normal β-cells, the β-cell forbidden genes; and (3) the likely upregulation of progenitor cell genes. These alterations lead to phenotypic reconfiguration of β-cells and ultimately defective insulin secretion. While the major role of glucotoxicity in β-cell dedifferentiation is well established, the precise mechanisms involved are still under investigation. This review highlights the identified molecular mechanisms implicated in β-cell dedifferentiation including oxidative stress, endoplasmic reticulum (ER) stress, inflammation and hypoxia. It discusses the role of Foxo1, Myc and inhibitor of differentiation proteins and underscores the emerging role of non-coding RNAs. Finally, it proposes a novel hypothesis of β-cell dedifferentiation as a potential adaptive mechanism to escape cell death under stress conditions.

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High glucose and hydrogen peroxide increase c-Myc and haeme-oxygenase 1 mRNA levels in rat pancreatic islets without activating NF?B

Cited by 61 publications

References 63 publications

Beta cell apoptosis in diabetes

Beta cell apoptosis in diabetes

Mechanisms of Pancreatic β-Cell Death in Type 1 and Type 2 Diabetes

Mechanisms of β-cell dedifferentiation in diabetes: recent findings and future research directions

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