ArticleDiabetes2010
Oxygen tension regulates pancreatic beta-cell differentiation through hypoxia-inducible factor 1alpha.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 113 citations in OpenAlex.
- Combination treatment of autologous bone marrow stem cell transplantation and hyperbaric oxygen therapy for type 2 diabetes mellitus: A randomized controlled trial.Cell transplantation · 2019Trial
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- βMedicinal research reviews · 2025Review
- Materials approaches for next-generation encapsulated cell therapies.MRS communications · 2025Review
- Beta-cell function in type 2 diabetes (T2DM): Can it be preserved or enhanced?Journal of diabetes · 2023Review
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- Fetal Oxygenation from the 23rd to the 36th Week of Gestation Evaluated through the Umbilical Cord Blood Gas Analysis.International journal of molecular sciences · 2023Article
- Islets in the body are never flat: transitioning from two-dimensional (2D) monolayer culture to three-dimensional (3D) spheroid for better efficiency in the generation of functional hPSC-derived pancreatic β cells in vitro.Cell communication and signaling : CCS · 2023Review
- Epigenetic Changes Induced by High Glucose in Human Pancreatic Beta Cells.Journal of diabetes research · 2023Article
- Fetal oxygenation in the last weeks of pregnancy evaluated through the umbilical cord blood gas analysis.Frontiers in pediatrics · 2023Article
- HIF-2α Preserves Mitochondrial Activity and Glucose Sensing in Compensating β-Cells in Obesity.Diabetes · 2022Article
- Optimization of an OScientific reports · 2022Article
- The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress.PloS one · 2022Article
- Leveraging the strengths of mice, human stem cells, and organoids to model pancreas development and diabetes.Frontiers in endocrinology · 2022Review
- Vitamin D Receptor-Dependent Protective Effect of Moderate Hypoxia in a Mouse Colitis Model.Frontiers in physiology · 2022Article
- Adapting Physiology in Functional Human Islet Organogenesis.Frontiers in cell and developmental biology · 2022Article
- Engineering islets from stem cells for advanced therapies of diabetes.Nature reviews. Drug discovery · 2021Review
- Drivers of transcriptional variance in human intestinal epithelial organoids.Physiological genomics · 2021Article
- Disruption of O-Linked N-Acetylglucosamine Signaling in Placenta Induces Insulin Sensitivity in Female Offspring.International journal of molecular sciences · 2021Article
- Molecular mechanisms of transcription factor mediated cell reprogramming: conversion of liver to pancreas.Biochemical Society transactions · 2021Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveRecent evidence indicates that low oxygen tension (pO2) or hypoxia controls the differentiation of several cell types during development. Variations of pO2 are mediated through the hypoxia-inducible factor (HIF), a crucial mediator of the adaptative response of cells to hypoxia. The aim of this study was to investigate the role of pO2 in beta-cell differentiation. RESEARCH DESIGN AND
methodsWe analyzed the capacity of beta-cell differentiation in the rat embryonic pancreas using two in vitro assays. Pancreata were cultured either in collagen or on a filter at the air/liquid interface with various pO2. An inhibitor of the prolyl hydroxylases, dimethyloxaloylglycine (DMOG), was used to stabilize HIF1alpha protein in normoxia.
resultsWhen cultured in collagen, embryonic pancreatic cells were hypoxic and expressed HIF1alpha and rare beta-cells differentiated. In pancreata cultured on filter (normoxia), HIF1alpha expression decreased and numerous beta-cells developed. During pancreas development, HIF1alpha levels were elevated at early stages and decreased with time. To determine the effect of pO2 on beta-cell differentiation, pancreata were cultured in collagen at increasing concentrations of O2. Such conditions repressed HIF1alpha expression, fostered development of Ngn3-positive endocrine progenitors, and induced beta-cell differentiation by O2 in a dose-dependent manner. By contrast, forced expression of HIF1alpha in normoxia using DMOG repressed Ngn3 expression and blocked beta-cell development. Finally, hypoxia requires hairy and enhancer of split (HES)1 expression to repress beta-cell differentiation.
conclusionsThese data demonstrate that beta-cell differentiation is controlled by pO2 through HIF1alpha. Modifying pO2 should now be tested in protocols aiming to differentiate beta-cells from embryonic stem cells.
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