ArticleJCI insight2022
14-3-3ζ Constrains insulin secretion by regulating mitochondrial function in pancreatic β cells.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Hippocampal Mitochondrial Dysfunction and Synaptic Disruption Link Organophosphate Exposure to Pre-Diabetes: An LC-MS/MS-Based Proteomics Approach.Biomolecules · 2026Article
- Retinal vasculature-derived proteins serve as potential systemic biomarkers for diabetic retinopathy.BMJ open ophthalmology · 2026Article
- Proteomic analyses of human islets reveal potential markers of β cell dysfunction during prediabetes.JCI insight · 2026Article
- Review
- Normalization Challenges Across Adipocyte Differentiation and Lipid-Modulating Treatments: Identifying Reliable Housekeeping Genes.International journal of molecular sciences · 2026Article
- Adipocyte-specific ablation of plakoglobin in mice does not affect adiposity but results in sexual-dimorphic effects on weight gain.Physiological reports · 2025Article
- 14-3-3ζ allows for adipogenesis by modulating chromatin accessibility during the early stages of adipocyte differentiation.Molecular metabolism · 2025Article
- Signal transduction pathways controllingiScience · 2025Article
- Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity.Nature communications · 2025Article
- Hyperglucagonemia and glucagon hypersecretion in early type 2 diabetes result from multifaceted dysregulation of pancreatic mouse α-cells.Pflugers Archiv : European journal of physiology · 2025Article
- The Interaction between miRNAs and 14-3-3ζ Protein in Different Diseases.Protein and peptide letters · 2025Review
- Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity.bioRxiv : the preprint server for biology · 2024Article
- Plasma proteomics in children with new-onset type 1 diabetes identifies new potential biomarkers of partial remission.Scientific reports · 2024Article
- The Development of CDC25A-Derived Phosphoseryl Peptides That Bind 14-3-3ε with High Affinities.International journal of molecular sciences · 2024Article
- Article
- Nucleo-cytoplasmic shuttling of 14-3-3 epsilon carrying hnRNP C promotes autophagy.Cancer biology & therapy · 2023Article
- Is 14-3-3 the Combination to Unlock New Pathways to Improve Metabolic Homeostasis and β-Cell Function?Diabetes · 2023Review
- Article
- PEPITEM modulates leukocyte trafficking to reduce obesity-induced inflammation.Clinical and experimental immunology · 2023Article
- Recent Developments in Islet Biology: A Review With Patient Perspectives.Canadian journal of diabetes · 2023Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 4 countries.
Funding
Abstract
While critical for neurotransmitter synthesis, 14-3-3 proteins are often assumed to have redundant functions due to their ubiquitous expression, but despite this assumption, various 14-3-3 isoforms have been implicated in regulating metabolism. We previously reported contributions of 14-3-3ζ in β cell function, but these studies were performed in tumor-derived MIN6 cells and systemic KO mice. To further characterize the regulatory roles of 14-3-3ζ in β cell function, we generated β cell-specific 14-3-3ζ-KO mice. Although no effects on β cell mass were detected, potentiated glucose-stimulated insulin secretion (GSIS), mitochondrial function, and ATP synthesis were observed. Deletion of 14-3-3ζ also altered the β cell transcriptome, as genes associated with mitochondrial respiration and oxidative phosphorylation were upregulated. Acute 14-3-3 protein inhibition in mouse and human islets recapitulated the enhancements in GSIS and mitochondrial function, suggesting that 14-3-3ζ is the critical isoform in β cells. In dysfunctional db/db islets and human islets from type 2 diabetic donors, expression of Ywhaz/YWHAZ, the gene encoding 14-3-3ζ, was inversely associated with insulin secretion, and pan-14-3-3 protein inhibition led to enhanced GSIS and mitochondrial function. Taken together, this study demonstrates important regulatory functions of 14-3-3ζ in the regulation of β cell function and provides a deeper understanding of how insulin secretion is controlled in β cells.
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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 Socratic graph.