ArticleCell death & disease2012
Acute hypoxia induces apoptosis of pancreatic β-cell by activation of the unfolded protein response and upregulation of CHOP.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed.
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- A dual-functional injectable polysaccharide hydrogel incorporating oxygen-carrying nanoemulsion and VEGF for enhancing islet survival and glycemic control in diabetic mice.Regenerative biomaterials · 2026Article
- Review
- From cold chain to ambient: Benefits, risks, and evidence across cell therapy logistics.Molecular therapy. Methods & clinical development · 2025Review
- Engineering hypoimmune stem cell-derived beta cells.Stem cell research & therapy · 2025Review
- Improving cellular fitness of human stem cell-derived islets under hypoxia.Nature communications · 2025Article
- Serum glucose/potassium ratio as an indicator of early and delayed outcomes of acute carbon monoxide poisoning.Toxicology research · 2024Article
- Hypoxia-induced cysteine metabolism reprogramming is crucial for the tumorigenesis of colorectal cancer.Redox biology · 2024Article
- Roles of β-Cell Hypoxia in the Progression of Type 2 Diabetes.International journal of molecular sciences · 2024Review
- Status of islet transplantation and innovations to sustainable outcomes: novel sites, cell sources, and drug delivery strategies.Frontiers in transplantation · 2024Review
- Machine learning chained neural network analysis of oxygen transport amplifies the physiological relevance of vascularized microphysiological systems.Bioengineering & translational medicine · 2023Article
- Hypoxia causes pancreatic β-cell dysfunction and impairs insulin secretion by activating the transcriptional repressor BHLHE40.EMBO reports · 2023Article
- Review
- Extracellular vesicle-mediated intercellular and interorgan crosstalk of pancreatic islet in health and diabetes.Frontiers in endocrinology · 2023Review
- Single-cell RNA-seq transcriptomic landscape of human and mouse islets and pathological alterations of diabetes.iScience · 2022Article
- COVID-19 and diabetes: What do we know so far?Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Cholecystokinin attenuates β-cell apoptosis in both mouse and human islets.Translational research : the journal of laboratory and clinical medicine · 2022Article
- Risks of Developing Diabetes and Hyperglycemic Crisis Following Carbon Monoxide Poisoning: A Study Incorporating Epidemiologic Analysis and Animal Experiment.Clinical epidemiology · 2022Article
- Immunometabolic bases of type 2 diabetes in the severity of COVID-19.World journal of diabetes · 2021Review
- Redox Homeostasis in Pancreatic β-Cells: From Development to Failure.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The success of pancreatic β-cells transplantation to treat type 1 diabetes has been hindered by massive β-cell dysfunction and loss of β-cells that follows the procedure. Hypoxia-mediated cell death has been considered one of the main difficulties that must be overcome for transplantation to be regarded as a reliable therapy. Here we have investigated the mechanisms underlying β-cell death in response to hypoxia (1% O(2)). Our studies show that mouse insulinoma cell line 6 (Min6) cells undergo apoptosis with caspase-3 activation occurring as early as 2 h following exposure to hypoxia. Hypoxia induces endoplasmic reticulum stress in Min6 cells leading to activation of the three branches of the unfolded protein response pathway. In response to hypoxia the pro-apoptotic transcription factor C/EBP homologous protein (CHOP) is upregulated. The important role of CHOP in the apoptotic process was highlighted by the rescue of Min6 cells from hypoxia-mediated apoptosis observed in CHOP-knockdown cells. Culturing isolated pancreatic mouse islets at normoxia showed intracellular hypoxia with accumulation of hypoxia-inducible factor-1α and upregulation of CHOP, the latter one occurring as early as 4 h after isolation. Finally, we observed that pancreatic islets of type 2 db/db diabetic mice were more hypoxic than their counterpart in normoglycemic animals. This finding indicates that hypoxia-mediated apoptosis may occur in type 2 diabetes.
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