ArticleMolecular endocrinology (Baltimore, Md.)2011
PERK activation at low glucose concentration is mediated by SERCA pump inhibition and confers preemptive cytoprotection to pancreatic β-cells.
Article in Molecular endocrinology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
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- Redox regulation of UPR signalling and mitochondrial ER contact sites.Cellular and molecular life sciences : CMLS · 2024Review
- Tumor microenvironment signaling and therapeutics in cancer progression.Cancer communications (London, England) · 2023Review
- Deletion of the Unfolded Protein Response Transducer IRE1α Is Detrimental to Aging Photoreceptors and to ER Stress-Mediated Retinal Degeneration.Investigative ophthalmology & visual science · 2023Article
- The Proteostasis Network: A Global Therapeutic Target for Neuroprotection after Spinal Cord Injury.Cells · 2022Review
- The Role of the Hypoxia-Related Unfolded Protein Response (UPR) in the Tumor Microenvironment.Cancers · 2022Review
- Uncoupling protein 2 and aldolase B impact insulin release by modulating mitochondrial function and CaiScience · 2022Article
- Living Dangerously: Protective and Harmful ER Stress Responses in Pancreatic β-Cells.Diabetes · 2021Review
- Endoplasmic reticulum stress signals in the tumour and its microenvironment.Nature reviews. Cancer · 2021Review
- Chinese Herbal Medicine Alleviates Myocardial Ischemia/Reperfusion Injury by Regulating Endoplasmic Reticulum Stress.Evidence-based complementary and alternative medicine : eCAM · 2021Review
- News from Mars: Two-Tier Paradox, Intracellular PCR, Chimeric Junction Shift, Dark Matter mRNA and Other Remarkable Features of Mammalian RNA-Dependent mRNA Amplification. Implications for Alzheimer's Disease, RNA-Based Vaccines and mRNA Therapeutics.Annals of integrative molecular medicine · 2021Article
- Calcium Signaling in ß-cell Physiology and Pathology: A Revisit.International journal of molecular sciences · 2019Review
- mTOR is a Key Protein Involved in the Metabolic Effects of Simple Sugars.International journal of molecular sciences · 2019Review
- Friend and foe: β-cell CaMolecular metabolism · 2019Review
- Article
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5 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinase R-like ER kinase (PERK) is activated at physiologically low glucose concentrations in pancreatic β-cells. However, the molecular mechanisms by which PERK is activated under these conditions and its role in β-cell function are poorly understood. In this report, we investigated, in dispersed rat islets of Langerhans and mouse insulinoma-6 (MIN6) cells, the relationship between extracellular glucose concentration, the free endoplasmic reticulum (ER) calcium concentration ([Ca(2+)](ER)) measured directly using an ER targeted fluorescence resonance energy transfer-based calcium sensor, and the activation of PERK. We found that a decrease in glucose concentration leads to a concentration-dependent reduction in [Ca(2+)](ER) that parallels the activation of PERK and the phosphorylation of its substrate eukaryotic initiation factor-2α. We provide evidence that this decrease in [Ca(2+)](ER) is caused by a decrease in sarcoplasmic/ER Ca(2+)-ATPase pump activity mediated by a reduction in the energy status of the cell. Importantly, we also report that PERK-dependent eukaryotic initiation factor-2α phosphorylation at low glucose concentration plays a significant role in 1) the regulation of both proinsulin and global protein synthesis, 2) cell viability, and 3) conferring preemptive cytoprotection against ER stress. Taken together, these results provide evidence that a decrease in the ATP/energy status of the cell in response to a decrease in glucose concentration results in sarcoplasmic/ER Ca(2+)-ATPase pump inhibition, the efflux of Ca(2+) from the ER, and the activation of PERK, which plays an important role in both pancreatic β-cell function and survival.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.