ArticleScientific reports2016
IRS1 deficiency protects β-cells against ER stress-induced apoptosis by modulating sXBP-1 stability and protein translation.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Effects of Genistein on Inflammasome Induced Pancreatic β-Cell Apoptosis by Dexamethasone.Molecular nutrition & food research · 2025Article
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- Disrupted Endoplasmic Reticulum CaBiology · 2024Review
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- The activation of spliced X-box binding protein 1 by isorhynchophylline therapy improves diabetic encephalopathy.Cell biology and toxicology · 2023Article
- XBP1 maintains beta cell identity, represses beta-to-alpha cell transdifferentiation and protects against diabetic beta cell failure during metabolic stress in mice.Diabetologia · 2022Article
- Apigetrin ameliorates streptozotocin-induced pancreatic β-cell damages via attenuating endoplasmic reticulum stress.In vitro cellular & developmental biology. Animal · 2020Article
- Novel roles of ER stress in repressing neural activity and seizures through Mdm2- and p53-dependent protein translation.PLoS genetics · 2019Article
- Lipotoxicity andJournal of the Endocrine Society · 2019Review
- The IRE1α-XBP1s pathway promotes insulin-stimulated glucose uptake in adipocytes by increasing PPARγ activity.Experimental & molecular medicine · 2018Article
- The transformics assay: first steps for the development of an integrated approach to investigate the malignant cell transformation in vitro.Carcinogenesis · 2018Article
- Review
- β-Cell Autophagy in Diabetes Pathogenesis.Endocrinology · 2018Review
- The Effect of Amygdalin on Endoplasmic Reticulum (ER) Stress Induced Hepatic Steatosis in Mice.The Malaysian journal of medical sciences : MJMS · 2018Article
- Temporal characterization of β cell-adaptive and -maladaptive mechanisms during chronic high-fat feeding in C57BL/6NTac mice.The Journal of biological chemistry · 2017Article
- Inhibition of Reticulon-1A-Mediated Endoplasmic Reticulum Stress in Early AKI Attenuates Renal Fibrosis Development.Journal of the American Society of Nephrology : JASN · 2017Article
- Insulin receptor substrate 1, but not IRS2, plays a dominant role in regulating pancreatic alpha cell function in mice.The Journal of biological chemistryArticle
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Endoplasmic reticulum (ER) stress is among several pathological features that underlie β-cell failure in the development of type 1 and type 2 diabetes. Adaptor proteins in the insulin/insulin-like-growth factor-1 signaling pathways, such as insulin receptor substrate-1 (IRS1) and IRS2, differentially impact β-cell survival but the underlying mechanisms remain unclear. Here we report that β-cells deficient in IRS1 (IRS1KO) are resistant, while IRS2 deficiency (IRS2KO) makes them susceptible to ER stress-mediated apoptosis. IRS1KOs exhibited low nuclear accumulation of spliced XBP-1 due to its poor stability, in contrast to elevated accumulation in IRS2KO. The reduced nuclear accumulation in IRS1KO was due to protein instability of Xbp1 secondary to proteasomal degradation. IRS1KO also demonstrated an attenuation in their general translation status in response to ER stress revealed by polyribosomal profiling. Phosphorylation of eEF2 was dramatically increased in IRS1KO enabling the β-cells to adapt to ER stress by blocking translation. Furthermore, significantly high ER calcium (Ca(2+)) was detected in IRS1KO β-cells even upon induction of ER stress. These observations suggest that IRS1 could be a therapeutic target for β-cell protection against ER stress-mediated cell death by modulating XBP-1 stability, protein synthesis, and Ca(2+) storage in the ER.
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