Selective Inhibition of Eukaryotic Translation Initiation Factor 2α Dephosphorylation Potentiates Fatty Acid-induced Endoplasmic Reticulum Stress and Causes Pancreatic β-Cell Dysfunction and Apoptosis
Miriam Cnop,Miriam Cnop,Laurence Ladrière,Paul Hekerman,Fernanda Ortis,Alessandra K Cardozo,Zeynep Dogusan,Daisy Flamez,Michael Boyce,Junying Yuan,Decio L. Eizirik +10 more
TLDR
It is demonstrated that excessive eIF2α phosphorylation is poorly tolerated by β-cells and exacerbates free fatty acid-induced apoptosis, which modifies the present paradigm regarding the beneficial role of eIF 2 α phosphorylated cells and must be taken into consideration when designing therapies to protect β- cells in type 2 diabetes.About:
This article is published in Journal of Biological Chemistry.The article was published on 2006-12-08 and is currently open access. It has received 290 citations till now. The article focuses on the topics: Salubrinal & Endoplasmic reticulum.read more
Citations
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Journal ArticleDOI
Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease
TL;DR: The endoplasmic reticulum is the major site in the cell for protein folding and trafficking and is central to many cellular functions and is emerging as a potential site for the intersection of inflammation and metabolic disease.
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Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities
Inki Kim,Wenjie Xu,John C. Reed +2 more
TL;DR: The accumulation of unfolded proteins in the endoplasmic reticulum represents a cellular stress induced by multiple stimuli and pathological conditions, which triggers an evolutionarily conserved series of signal-transduction events, which constitutes the unfolded protein response.
Journal ArticleDOI
The role for endoplasmic reticulum stress in diabetes mellitus.
TL;DR: This review addresses the transition from physiology to pathology, namely how and why the physiological UPR evolves to a proapoptotic ER stress response and which defenses are triggered by beta-cells against these challenges.
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Endoplasmic Reticulum Stress in Disease Pathogenesis
TL;DR: A selection of diseases whose pathogenesis involves ER stress is discussed and an intricate set of signaling pathways from the ER to the cytosol and nucleus are discussed, to allow the cell to respond to the presence of misfolded proteins within the ER.
Journal ArticleDOI
Activation of mTORC2 by Association with the Ribosome
TL;DR: Findings with melanoma and colon cancer cells suggest that mTORC2-ribosome association is important in oncogenic PI3K signaling, suggesting that TORC2 is active only in growing cells.
References
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β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes
Alexandra E. Butler,Juliette Janson,Susan Bonner-Weir,Robert A. Ritzel,Robert A. Rizza,Peter C. Butler +5 more
TL;DR: Since the major defect leading to a decrease in β-cell mass in type 2 diabetes is increased apoptosis, while new islet formation andβ-cell replication are normal, therapeutic approaches designed to arrest apoptosis could be a significant new development in the management of type 2 Diabetes.
Journal ArticleDOI
XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription Factor
TL;DR: The transcription factor XBP1, a target of ATF6, is identified as a mammalian substrate of such an unconventional mRNA splicing system and it is shown that only the spliced form of X BP1 can activate the UPR efficiently.
Journal ArticleDOI
Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
Umut Ozcan,Qiong Cao,Erkan Yilmaz,Ann-Hwee Lee,Neal N. Iwakoshi,Esra Özdelen,Gurol Tuncman,Cem Z. Görgün,Laurie H. Glimcher,Gökhan S. Hotamisligil +9 more
TL;DR: It is shown that obesity causes endoplasmic reticulum (ER) stress, which leads to suppression of insulin receptor signaling through hyperactivation of c-Jun N-terminal kinase (JNK) and subsequent serine phosphorylation of insulin receptors substrate–1 (IRS-1).
Journal ArticleDOI
Endoplasmic reticulum stress: cell life and death decisions
TL;DR: Important roles for ER-initiated cell death pathways have been recognized for several diseases, including hypoxia, ischemia/reperfusion injury, neurodegeneration, heart disease, and diabetes.
Journal ArticleDOI
CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum
Helene Zinszner,Masahiko Kuroda,Xiaozhong Wang,Nikoleta Batchvarova,Richard T. Lightfoot,Helen Remotti,James L. Stevens,David Ron +7 more
TL;DR: Compared with the wild type, mouse embryonic fibroblasts derived from chop -/- animals exhibited significantly less programmed cell death when challenged with agents that perturb ER function, and the proximal tubule epithelium of chop -/+ animals exhibited fourfold lower levels of TUNEL-positive cells, and significantly less evidence for subsequent regeneration.
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The role for endoplasmic reticulum stress in diabetes mellitus.
Signal integration in the endoplasmic reticulum unfolded protein response
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