The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Selective Inhibition of Eukaryotic Translation Initiation Factor 2α Dephosphorylation Potentiates Fatty Acid-induced Endoplasmic Reticulum Stress and Causes Pancreatic β-Cell Dysfunction and Apoptosis
Open accessAbstract
Free fatty acids cause pancreatic beta-cell apoptosis and may contribute to beta-cell loss in type 2 diabetes via the induction of endoplasmic reticulum stress. Reductions in eukaryotic translation initiation factor (eIF) 2alpha phosphorylation trigger beta-cell failure and diabetes. Salubrinal selectively inhibits eIF2alpha dephosphorylation, protects other cells against endoplasmic reticulum stress-mediated apoptosis, and has been proposed as a beta-cell protector. Unexpectedly, salubrinal induced apoptosis in primary beta-cells, and it potentiated the deleterious effects of oleate and palmitate. Salubrinal induced a marked eIF2alpha phosphorylation and potentiated the inhibitory effects of free fatty acids on protein synthesis and insulin release. The synergistic activation of the PERK-eIF2alpha branch of the endoplasmic reticulum stress response, but not of the IRE1 and activating transcription factor-6 pathways, led to a marked induction of activating transcription factor-4 and the pro-apoptotic transcription factor CHOP. Our findings demonstrate that excessive eIF2alpha phosphorylation is poorly tolerated by beta-cells and exacerbates free fatty acid-induced apoptosis. This modifies the present paradigm regarding the beneficial role of eIF2alpha phosphorylation in beta-cells and must be taken into consideration when designing therapies to protect beta-cells in type 2 diabetes.
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Cites
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β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes
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Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
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Endoplasmic reticulum stress: cell life and death decisions
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Mechanisms of Pancreatic β-Cell Death in Type 1 and Type 2 Diabetes
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Self-citationA Selective Inhibitor of eIF2α Dephosphorylation Protects Cells from ER Stress
Boyce, M., Bryant, K. F., Jousse, C., Long, K., Harding, H. P., Scheuner, D., Kaufman, R. J., Ma, D., Coen, D. M., Ron, D., et al. (2005) · Science · doi:10.1126/science.1101902 · Cited by 1,403
Self-citationFeedback Inhibition of the Unfolded Protein Response by GADD34-Mediated Dephosphorylation of eIF2α
Novoa, I., Zeng, H., Harding, H. P., & Ron, D. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.153.5.1011 · Cited by 1,386
Cited by
Endoplasmic reticulum stress and the inflammatory basis of metabolic disease
Hotamisligil, G. S. (2010) · Cell · doi:10.1016/j.cell.2010.02.034 · Cited by 2,802
The Role for Endoplasmic Reticulum Stress in Diabetes Mellitus
Eizirik, D. L., Cardozo, A. K., & Cnop, M. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0015 · Cited by 1,173
Self-citationPancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure
Eizirik, D. L., Pasquali, L., & Cnop, M. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0355-7 · Cited by 854
Self-citationGregor, M. F., & Hotamisligil, G. S. (2007) · Journal of Lipid Research · doi:10.1194/jlr.r700007-jlr200 · Cited by 586
Endoplasmic Reticulum Stress: Signaling the Unfolded Protein Response
Lai, E., Teodoro, T., & Volchuk, A. (2007) · Physiology · doi:10.1152/physiol.00050.2006 · Cited by 478
Metadata
- Authors
- Cnop, M., Ladriere, L., Hekerman, P., Ortis, F., Cardozo, A. K., Dogusan, Z., Flamez, D., Boyce, M., Yuan, J., & Eizirik, D. L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 282
- Issue
- 6
- Pages
- 3989-3997
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1967659527
- Cited by
- 289
- References
- 57
- FWCI
- 7.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Selective Inhibition of Eukaryotic Translation Initiation Factor 2α Dephosphorylation Potentiates Fatty Acid-induced Endoplasmic Reticulum Stress and Causes Pancreatic β-Cell Dysfunction and Apoptosis. https://app.cochat.ai/papers/10.1074/jbc.m607627200
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- Cnop, M., Ladriere, L., Hekerman, P., Ortis, F., Cardozo, A. K., Dogusan, Z., Flamez, D., Boyce, M., Yuan, J., & Eizirik, D. L. (2007). Selective Inhibition of Eukaryotic Translation Initiation Factor 2α Dephosphorylation Potentiates Fatty Acid-induced Endoplasmic Reticulum Stress and Causes Pancreatic β-Cell Dysfunction and Apoptosis. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m607627200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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