Dynamin-related protein 1 is implicated in endoplasmic reticulum stress-induced pancreatic β-cell apoptosis

Peng, Liang; Men, Xiuli; Zhang, Wenjian; Wang, Haiyan; Xu, Shiqing; Xu, Mei; Xu, Yang; Yang, Wenying; Lou, Jinning

doi:10.3892/ijmm.2011.684

Cited by 13 publications

(9 citation statements)

References 29 publications

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“…The importance of mitochondrial dynamics in apoptosis in beta-cells is revealed by data demonstrating that preservation of mitochondrial morphology protects from nutrient-induced apoptosis. As well as evidence demonstrating that Drp1 mediates beta-cell apoptosis in response to high glucose and ER stress (24,25). Prolonged periods of high glucose in INS-1 cells induce both Drp1 and cytochrome c expression (25).…”

Section: Beta-cell Mitochondrial Dynamics Are Sensitive To High Nutrimentioning

confidence: 96%

“…Disruption of steady state fusion or fission in beta-cells has been shown to disrupt mitochondrial morphology and function thereby influencing beta-cell function under control conditions. Induction of a pro-fission state with overexpression of Drp1 increased ROS production, decreased GSIS by approximately 20%, and increased apoptosis in INS-1 cells (24,25). Furthermore, overexpression of hFis1 in INS-1 cells has been shown to reduce the amount of ATP that is produced at basal and stimulatory glucose concentrations.…”

Section: Disruptions In Mitochondrial Fusion and Fission Alter Beta-cmentioning

confidence: 99%

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Mitochondrial dynamics and morphology in beta-cells

Stiles

Shirihai

2012

Best Practice & Research Clinical Endocrinology & Metab

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Mitochondrial dynamics contribute to the regulation of mitochondrial shape as well as various mitochondrial functions and quality control. This is of particular interest in the beta-cell because of the key role mitochondria play in the regulation of beta-cell insulin secretion function. Moreover, mitochondrial dysfunction has been suggested to contribute to the development of Type 2 Diabetes. Genetic tools that shift the balance of mitochondrial fusion and fission result in alterations to beta-cell function and viability. Additionally, conditions that induce beta-cell dysfunction, such as exposure to a high nutrient environment, disrupt mitochondrial morphology and dynamics. While it has been shown that mitochondria display a fragmented morphology in islets of diabetic patients and animal models, the mechanism behind this is currently unknown. Here, we review the current literature on mitochondrial morphology and dynamics in the beta-cell as well as some of the unanswered question in this field.

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Section: Beta-cell Mitochondrial Dynamics Are Sensitive To High Nutrimentioning

confidence: 96%

Section: Disruptions In Mitochondrial Fusion and Fission Alter Beta-cmentioning

confidence: 99%

Mitochondrial dynamics and morphology in beta-cells

Stiles

Shirihai

2012

Best Practice & Research Clinical Endocrinology & Metab

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“…Additionally, short, high-dose incubations of hydrogen peroxide [92] and palmitate [93] induce mitochondrial fragmentation in C2C12 myotubes. Mitochondrial fission can increase mitochondrial uncoupling to ameliorate ROS production [94] as well as stimulate mitophagy [95, 96] and apoptosis [97–100] in order to let the cell adapt and respond to these major stressors.…”

Section: Mitochondrial Stress Signalsmentioning

confidence: 99%

Mitochondrial Stress Signaling Promotes Cellular Adaptations

Barbour

Turner

2014

International Journal of Cell Biology

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Mitochondrial dysfunction has been implicated in the aetiology of many complex diseases, as well as the ageing process. Much of the research on mitochondrial dysfunction has focused on how mitochondrial damage may potentiate pathological phenotypes. The purpose of this review is to draw attention to the less well-studied mechanisms by which the cell adapts to mitochondrial perturbations. This involves communication of stress to the cell and successful induction of quality control responses, which include mitophagy, unfolded protein response, upregulation of antioxidant and DNA repair enzymes, morphological changes, and if all else fails apoptosis. The mitochondrion is an inherently stressful environment and we speculate that dysregulation of stress signaling or an inability to switch on these adaptations during times of mitochondrial stress may underpin mitochondrial dysfunction and hence amount to pathological states over time.

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“…It has been known that mitochondrial fission and fusion modulators, dynamin-related protein 1 (Drp1) (12), optic atrophy protein 1 (Opa1) (13), prohibitin (14), and mitofusin (15), collectively control the dynamic balance of mitochondria fission and fusion processes and consequent mitochondria functions. Previous studies have demonstrated that Drp1 plays an important role in promoting hyperglycemia-induced apoptosis of β-cells and neurons (12,16,17). Drp1 expression was increased drastically in islet β-cells under hyperglycemia conditions.…”

mentioning

confidence: 99%

Rhein Protects Pancreatic β-Cells From Dynamin-Related Protein-1–Mediated Mitochondrial Fission and Cell Apoptosis Under Hyperglycemia

et al. 2013

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Rhein, an anthraquinone compound isolated from rhubarb, has been shown to improve glucose metabolism disorders in diabetic mice. The mechanism underlying the protective effect of rhein, however, remains unknown. Here, we demonstrate that rhein can protect the pancreatic β-cells against hyperglycemia-induced cell apoptosis through stabilizing mitochondrial morphology. Oral administration of rhein for 8 or 16 weeks in db/db mice significantly reduced fasting blood glucose (FBG) level and improved glucose tolerance. Cell apoptosis assay using both pancreatic sections and cultured pancreatic β-cells indicated that rhein strongly inhibited β-cell apoptosis. Morphological study showed that rhein was mainly localized at β-cell mitochondria and rhein could preserve mitochondrial ultrastructure by abolishing hyperglycemia-induced mitochondrial fission protein dynamin-related protein 1 (Drp1) expression. Western blot and functional analysis confirmed that rhein protected the pancreatic β-cells against hyperglycemia-induced apoptosis via suppressing mitochondrial Drp1 level. Finally, mechanistic study further suggested that decreased Drp1 level by rhein might be due to its effect on reducing cellular reactive oxygen species. Taken together, our study demonstrates for the first time that rhein can serve as a novel therapeutic agent for hyperglycemia treatment and rhein protects pancreatic β-cells from apoptosis by blocking the hyperglycemia-induced Drp1 expression.

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Dynamin-related protein 1 is implicated in endoplasmic reticulum stress-induced pancreatic β-cell apoptosis

Cited by 13 publications

References 29 publications

Mitochondrial dynamics and morphology in beta-cells

Mitochondrial dynamics and morphology in beta-cells

Mitochondrial Stress Signaling Promotes Cellular Adaptations

Rhein Protects Pancreatic β-Cells From Dynamin-Related Protein-1–Mediated Mitochondrial Fission and Cell Apoptosis Under Hyperglycemia

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