ArticleNature communications2022
Wnt4 is heterogeneously activated in maturing β-cells to control calcium signaling, metabolism and function.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Review
- Cellular signaling crosstalk between osteoporosis and diabetes: Common mechanisms and therapeutic targets (Review).Biomedical reports · 2026Review
- Epigenetic control of PDX1 and NGN3 by a computationally designed PRC2 inhibitor enforces pancreatic endocrine differentiation from pluripotent stem cells.Research square · 2026Article
- 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
- Development and validation of an interpretable machine learning model for predicting in-hospital hypoglycemia in adults with type 1 diabetes mellitus: a multicenter retrospective study.Frontiers in endocrinology · 2026Article
- Article
- Empagliflozin slows down natural kidney senescence via Six1/Wnt4/NF-κB pathway.Biogerontology · 2025Article
- Article
- Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors.Nature communications · 2025Article
- Diabetes-preventive molecular mechanisms of breast versus formula feeding: new insights into the impact of milk on stem cell Wnt signaling.Frontiers in nutrition · 2025Review
- Structure, interaction and nervous connectivity of beta cell primary cilia.Nature communications · 2024Article
- Generation and application of novel hES cell reporter lines for the differentiation and maturation of hPS cell-derived islet-like clusters.Scientific reports · 2024Article
- Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease.Cell metabolism · 2024Article
- Optogenetic β cell interrogation in vivo reveals a functional hierarchy directing the CaScience advances · 2024Article
- Article
- Heterozygous missense variant in GLI2 impairs human endocrine pancreas development.Nature communications · 2024Article
- Cell identity dynamics and insight into insulin secretagogues when employing stem cell-derived islets for disease modeling.Frontiers in bioengineering and biotechnology · 2024Article
- Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery.Frontiers in endocrinology · 2023Article
- Verapamil chronicles: advances from cardiovascular to pancreatic β-cell protection.Frontiers in pharmacology · 2023Review
- Therapeutic Strategies Targeting Pancreatic Islet β-Cell Proliferation, Regeneration, and Replacement.Endocrinology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetes is a multifactorial disorder characterized by loss or dysfunction of pancreatic β-cells. β-cells are heterogeneous, exhibiting different glucose sensing, insulin secretion and gene expression. They communicate with other endocrine cell types via paracrine signals and between β-cells via gap junctions. Here, we identify the importance of signaling between β-cells via the extracellular signal WNT4. We show heterogeneity in Wnt4 expression, most strikingly in the postnatal maturation period, Wnt4-positive cells, being more mature while Wnt4-negative cells are more proliferative. Knock-out in adult β-cells shows that WNT4 controls the activation of calcium signaling in response to a glucose challenge, as well as metabolic pathways converging to lower ATP/ADP ratios, thereby reducing insulin secretion. These results reveal that paracrine signaling between β-cells is important in addition to gap junctions in controling insulin secretion. Together with previous reports of WNT4 up-regulation in obesity our observations suggest an adaptive insulin response coordinating 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.