ArticleEMBO reports2023
Hypoxia causes pancreatic β-cell dysfunction and impairs insulin secretion by activating the transcriptional repressor BHLHE40.
Article in EMBO reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Review
- Hypoxia-responsive interaction between P-TEFb, BHLHE40, and Tim8-Tim13 regulates hypoxic gene transcription.Science advances · 2026Article
- Engineering the oxygen microenvironment for pancreatic islet transplants.NPJ Regenerative medicine · 2026Review
- Divergent cell-type specific hypoxia responses in human stem cell-derived and primary islets.Scientific reports · 2026Article
- Oxygen and glucose supplementation increases rates of linear growth and cell proliferation in growth-restricted fetal sheep.The Journal of physiology · 2026Article
- Molecular taxonomy of pancreatic neuroendocrine tumors reveals BEND2-fusions-driven transcriptional plasticity and therapeutic vulnerabilities.Cell reports. Medicine · 2026Article
- Oncometabolites and Hypoxia-Regulated Exosomes Shape HIF-Driven Macrophage Programs Across Type 2 Diabetes, Atherosclerosis, and Cancer.International journal of molecular sciences · 2026Review
- Bone Marrow Mesenchymal Stromal Cells and Their Derived Extracellular Vesicles Protect Pancreatic Beta-TC-6 Cells From Hypoxia-Induced Injury via miR-539-3p-Mediated Downregulation of CD36 Expression.Stem cells international · 2026Article
- Review
- Identification of type 2 diabetes- and obesity-associated human β-cells using deep transfer learning.eLife · 2025Article
- Effects of a Three-Day vs. Six-Day Exposure to Normobaric Hypoxia on the Cardiopulmonary Function of Rats.Current issues in molecular biology · 2025Article
- Interplay of hypoxia, immune dysregulation, and metabolic stress in pathophysiology of type 1 diabetes.Frontiers in immunology · 2025Review
- Clinical challenges and technological breakthroughs in helminthic therapy for diabetes.Frontiers in immunology · 2025Review
- IGF-II regulates lysyl oxidase propeptide and mediates its effects in part via basic helix-loop-helix E40.Matrix biology : journal of the International Society for Matrix Biology · 2024Article
- Single cell multiome profiling of pancreatic islets reveals physiological changes in cell type-specific regulation associated with diabetes risk.bioRxiv : the preprint server for biology · 2024Article
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Roles of β-Cell Hypoxia in the Progression of Type 2 Diabetes.International journal of molecular sciences · 2024Review
- Making mouse transcriptomics deconvolution accessible with immunedeconv.Bioinformatics advances · 2024Article
- TFEB and TFE3 control glucose homeostasis by regulating insulin gene expression.The EMBO journal · 2023Article
- Hypoxia causes pancreatic β-cell dysfunction and impairs insulin secretion by activating the transcriptional repressor BHLHE40.EMBO reports · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia can occur in pancreatic β-cells in type 2 diabetes. Although hypoxia exerts deleterious effects on β-cell function, the associated mechanisms are largely unknown. Here, we show that the transcriptional repressor basic helix-loop-helix family member e40 (BHLHE40) is highly induced in hypoxic mouse and human β-cells and suppresses insulin secretion. Conversely, BHLHE40 deficiency in hypoxic MIN6 cells or β-cells of ob/ob mice reverses defects in insulin secretion. Mechanistically, BHLHE40 represses the expression of Mafa, encoding the transcription factor musculoaponeurotic fibrosarcoma oncogene family A (MAFA), by attenuating the binding of pancreas/duodenum homeobox protein 1 (PDX1) to its enhancer region. Impaired insulin secretion in hypoxic β-cells was recovered by MAFA re-expression. Collectively, our work identifies BHLHE40 as a key hypoxia-induced transcriptional repressor in β-cells that inhibit insulin secretion by suppressing MAFA expression.
Indexed as
Identifiers
What Socratic holds
Registered trials
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 Socratic graph.