New insights into ER stress-induced insulin resistance

Flamment, Mélissa; Hajduch, Éric; Ferré, Pascal; Foufelle, Fabienne

doi:10.1016/j.tem.2012.06.003

Cited by 260 publications

(240 citation statements)

References 99 publications

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“…First strand cDNA was synthesized from 1 µg of total RNA employing the RevertAid First Strand cDNA Synthesis Kit (ThermoScientific, Loughborough, UK) and an oligo(dT) [12][13][14][15][16][17][18] primer as reverse primer. Then, target genes were amplified by real-time PCR using GoTaq qPCR Master Mix (Promega, Southampton, UK) in Applied Biosystems 7500 Real-Time PCR System (ThermoScientific, Loughborough, UK).…”

Section: Total Rna Isolation and Gene Expression Analysismentioning

confidence: 99%

“…The ER is the site of protein secreted synthesis and folding. Upon disruption in protein folding or modification within the ER, a state of stress ensues, resulting in the unfolded protein response (UPR) with the aim to return the ER to its physiological state and enhance cell survival [15][16][17]. The UPR functions via signalling through three stress-sensing proteins found on the ER membrane: PKR-like eukaryotic initiation factor 2α kinase (PERK), inositol-requiring kinase-1α (IRE-1α), and activating transcription factor (ATF)-6.…”

Section: Introductionmentioning

confidence: 99%

“…However, prolonged UPR activation leads to apoptosis, oxidative stress, and inflammation and is referred to as the "ER stress response". Diabetes results in metabolic conditions that increase the demand on the ER for protein and lipid synthesis [15]. Several studies including ours have shown that insulin resistant states such as obesity promote ER stress response in various tissues such as liver, adipose tissue, and the heart [13,18,19].…”

Section: Introductionmentioning

confidence: 99%

“…CHOP upregulates expression of pro-apoptotic proteins such as Bim, and downregulates expression of anti-apoptotic molecule Bcl-2 [16,17]. ER stress causes insulin resistance and participates in the low-grade inflammation observed in insulin resistant states [13,20] by mediating cell death and the activation of inflammatory pathways such as nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) [15]. An association between ER stress and endothelial dysfunction was reported in experimental models of diabetes [14,21]; however, the underpinning mechanisms are unclear especially regarding the role of ER-stress mediated inflammation and cell death.…”

Section: Introductionmentioning

confidence: 99%

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Heme oxygenase (HO)-1 induction prevents Endoplasmic Reticulum stress-mediated endothelial cell death and impaired angiogenic capacity

Maamoun

Zachariah

McVey

et al. 2017

Biochemical Pharmacology

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Most of diabetic cardiovascular complications are attributed to endothelial dysfunction and impaired angiogenesis. Endoplasmic Reticulum (ER) and oxidative stresses were shown to play a pivotal role in the development of endothelial dysfunction in diabetes.Hemeoxygenase-1 (HO-1) was shown to protect against oxidative stress in diabetes; however, its role in alleviating ER stress-induced endothelial dysfunction remains not fully elucidated. We aim here to test the protective role of HO-1 against high glucose-mediated ER stress and endothelial dysfunction and understand the underlying mechanisms with special emphasis on oxidative stress, inflammation and cell death. Altogether, we show here the critical role of ER stress-mediated cell death in diabetesinduced endothelial dysfunction and impaired angiogenesis and underscore the role of HO-1 induction as a key therapeutic modulator for ER stress response in ischemic disorders and diabetes. Our results also highlight the complex interplay between ER stress response and oxidative stress.

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Section: Total Rna Isolation and Gene Expression Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Heme oxygenase (HO)-1 induction prevents Endoplasmic Reticulum stress-mediated endothelial cell death and impaired angiogenic capacity

Maamoun

Zachariah

McVey

et al. 2017

Biochemical Pharmacology

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show abstract

“…To alleviate the deleterious effects of ROS, the PERK branch of the UPR can activate the transcription of several key antioxidant enzymes via the phosphorylation of nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) (Cullinan and Diehl 2006; Flamment et al. 2012). …”

Section: Introductionmentioning

confidence: 99%

Role of endoplasmic reticulum stress in drug‐induced toxicity

Foufelle

Fromenty

2016

Pharmacology Res & Perspec

Self Cite

194

161

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Drug‐induced toxicity is a key issue for public health because some side effects can be severe and life‐threatening. These adverse effects can also be a major concern for the pharmaceutical companies since significant toxicity can lead to the interruption of clinical trials, or the withdrawal of the incriminated drugs from the market. Recent studies suggested that endoplasmic reticulum (ER) stress could be an important event involved in drug liability, in addition to other key mechanisms such as mitochondrial dysfunction and oxidative stress. Indeed, drug‐induced ER stress could lead to several deleterious effects within cells and tissues including accumulation of lipids, cell death, cytolysis, and inflammation. After recalling important information regarding drug‐induced adverse reactions and ER stress in diverse pathophysiological situations, this review summarizes the main data pertaining to drug‐induced ER stress and its potential involvement in different adverse effects. Drugs presented in this review are for instance acetaminophen (APAP), arsenic trioxide and other anticancer drugs, diclofenac, and different antiretroviral compounds. We also included data on tunicamycin (an antibiotic not used in human medicine because of its toxicity) and thapsigargin (a toxic compound of the Mediterranean plant Thapsia garganica) since both molecules are commonly used as prototypical toxins to induce ER stress in cellular and animal models.

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Angiotensin converting enzyme 2: A new important player in the regulation of glycemia

2013

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In spite of the novel anti-diabetic drugs available on the market, type 2 diabetes mellitus (T2DM) affects nearly 25 million people in the USA and causes about 5% of all deaths globally each year. Given the rate and proportion by which T2DM is affecting human beings, it is indispensable to identify new therapeutic targets that can control the disease. Recent pre-clinical and clinical studies suggest that attenuating the activity of the renin-angiotensin system (RAS) could improve glycemia in diabetic patients. Angiotensin converting enzyme 2 (ACE2) counteracts RAS over-activity by degrading Ang-II, a vasoconstrictor, to Ang-(1-7) which is a vasodilator. A decrease in ACE2 and an increase in ADAM17-mediated shedding activity have been observed with the progression of T2DM suggesting the importance of this mechanism in the disease. Indeed, restoration of ACE2 improves glycemia in db/db and Ang-II-infused mice. The beneficial effects of ACE2 can be attributed to reduced oxidative stress and ADAM17 expression in the islets of Langerhans in addition to the improvement of blood flow to the β-cells. The advantage of ACE2 over other RAS blockers is that ACE2 not only counteracts the negative effects of Ang-II but also increases Ang-(1-7)/MasR [a receptor through which Ang-(1-7) produces its actions] signaling in the cells. Increased Ang-(1-7)/MasR signaling has been reported to improve insulin sensitivity and glycemia in diabetic animals. Altogether, ACE2/Ang-(1-7)/MasR axis of the RAS appears to be protective in T2DM and strategies to restore ACE2 levels in the disease seem to be a promising therapy for Ang-II-mediated T2DM.

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New insights into ER stress-induced insulin resistance

Cited by 260 publications

References 99 publications

Heme oxygenase (HO)-1 induction prevents Endoplasmic Reticulum stress-mediated endothelial cell death and impaired angiogenic capacity

Heme oxygenase (HO)-1 induction prevents Endoplasmic Reticulum stress-mediated endothelial cell death and impaired angiogenic capacity

Role of endoplasmic reticulum stress in drug‐induced toxicity

Angiotensin converting enzyme 2: A new important player in the regulation of glycemia

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