ArticleDiabetes2013
Npas4 is a novel activity-regulated cytoprotective factor in pancreatic β-cells.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
- Acute glucose stimulation drives coordinated translational reprogramming in primary pancreatic islets: from global remodeling to fine-tuned insulin synthesis.Frontiers in endocrinology · 2026Article
- Truncated CD19 as a selection marker for the isolation of stem cell-derived β-cells.Disease models & mechanisms · 2026Article
- Histology image analysis of 13 healthy tissues reveals molecular-histological correlations.Scientific reports · 2025Article
- VDAC1 is a target for pharmacologically induced insulin hypersecretion in β cells.Cell reports · 2025Article
- NPAS4 Depletion in POMC Neurons Protects From Obesity and Alters the Feeding-regulated Transcriptome in Male Mice.Endocrinology · 2025Article
- The role of bHLH-PAS transcription factors in endoplasmic reticulum stress.Frontiers in molecular biosciences · 2025Review
- An INSULIN and IAPP dual reporter enables tracking of functional maturation of stem cell-derived insulin producing cells.Molecular metabolism · 2024Article
- Type 2 diabetes susceptibility gene GRK5 regulates physiological pancreatic β-cell proliferation via phosphorylation of HDAC5.iScience · 2023Article
- Pancreatic islet cell type-specific transcriptomic changes during pregnancy and postpartum.iScience · 2023Article
- Structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers reveal new dimerization modalities in the bHLH-PAS transcription factor family.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Calcium-dependent transcriptional changes in human pancreatic islet cells reveal functional diversity in islet cell subtypes.Diabetologia · 2022Article
- Long non-coding RNAs: a valuable biomarker for metabolic syndrome.Molecular genetics and genomics : MGG · 2022Review
- Small Molecule-mediated Insulin Hypersecretion Induces Transient ER Stress Response and Loss of Beta Cell Function.Endocrinology · 2022Article
- The Wnt signaling receptor Fzd9 is essential for Myc-driven tumorigenesis in pancreatic islets.Life science alliance · 2021Article
- The Participation of the Intrinsically Disordered Regions of the bHLH-PAS Transcription Factors in Disease Development.International journal of molecular sciences · 2021Article
- The role of α-ketoglutarate and the hypoxia sensing pathway in the regulation of pancreatic β-cell function.Islets · 2020Review
- Lrrc55 is a novel prosurvival factor in pancreatic islets.American journal of physiology. Endocrinology and metabolism · 2019Article
- Subcellular Localization Signals of bHLH-PAS Proteins: Their Significance, Current State of Knowledge and Future Perspectives.International journal of molecular sciences · 2019Review
- Friend and foe: β-cell CaMolecular metabolism · 2019Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Cellular homeostasis requires intrinsic sensing mechanisms to temper function in the face of prolonged activity. In the pancreatic β-cell, glucose is likely a physiological trigger that activates an adaptive response to stimulation, thereby maintaining cellular homeostasis. Immediate early genes (IEGs) are activated as a first line of defense in cellular homeostasis and are largely responsible for transmitting an environmental cue to a cellular response. Here we examine the regulation and function of the novel β-cell IEG, neuronal PAS domain protein 4 (Npas4). Using MIN6 cells, mouse and human islets, as well as in vivo infusions, we demonstrate that Npas4 is expressed within pancreatic islets and is upregulated by β-cell depolarizing agents. Npas4 tempers β-cell function through a direct inhibitory interaction with the insulin promoter and by blocking the potentiating effects of GLP-1 without significantly reducing glucose-stimulated secretion. Finally, Npas4 expression is induced by classical endoplasmic reticulum (ER) stressors and can prevent thapsigargin- and palmitate-induced dysfunction and cell death. These results suggest that Npas4 is a key activity-dependent regulator that improves β-cell efficiency in the face of stress. We posit that Npas4 could be a novel therapeutic target in type 2 diabetes that could both reduce ER stress and cell death and maintain basal cell function.
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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 OpenQuestion graph.