ArticleNature medicine2015
Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers.
What it found
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Who cites it
170 citing papers in PubMed, 256 citations in OpenAlex.
- BAF60A governs beta cell identity to control systemic glucose homeostasis.Diabetologia · 2026Article
- The comparative cell physiology of stem cell-derived and primary human β cells.Nature reviews. Endocrinology · 2026Review
- Somatostatin receptors shape insulin and glucagon output within the pancreatic islet in mice through direct and paracrine effects.Diabetologia · 2026Article
- Intra-Islet Paracrine Regulation of Glucagon Secretion During Hypoglycemia, Euglycemia, and Hyperglycemia.Annals of the New York Academy of Sciences · 2026Review
- The paracrine signalling between endothelial and pancreatic β-cells: implications for oxidative stress and diabetes.Journal of endocrinological investigation · 2026Review
- Pancreatic α-cells are functionally heterogeneous and sex-dependently regulated by neighboring endocrine cells.Communications biology · 2026Article
- Article
- Endocrine-disrupting chemical exposure during differentiation alters the proliferation-maturation balance in stem-cell islets.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Antecedent hypoglycaemia impairs glucagon secretion by enhancing somatostatin-mediated negative feedback control.Nature metabolism · 2026Article
- The metabolic role of corticotropin-releasing hormone receptor 2 and its UCN peptides: emerging therapeutic potential.Skeletal muscle · 2025Review
- Somatostatin Receptors Shape Insulin and Glucagon Output within the Pancreatic Islet through Direct and Paracrine Effects.bioRxiv : the preprint server for biology · 2025Article
- From Human to Mouse and Back Again: Genetic and Genomic Ta(i)les of Islet Dysfunction in Type 2 Diabetes.Annual review of genetics · 2025Review
- Pancreatic Cancer and Diabetes: Insights, Hypotheses, and Next Steps.International journal of molecular sciences · 2025Review
- Heterogeneity in the coordination of delta cells with beta cells is driven by both paracrine signals and low-density Cx36 gap junctions.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Islet hormones at the intersection of glucose and amino acid metabolism.Nature reviews. Endocrinology · 2025Review
- FXYD2 marks and regulates maturity of β cells via ion channel-mediated signal transduction.Nature communications · 2025Article
- Re-evaluating Intra-Islet Paracrine Signaling: Precision, Pulsatility and the Path toward Mechanistic Clarity.Journal of biomedical research & environmental sciences · 2025Article
- β-Cell Dedifferentiation in HOMA-βlow and HOMA-βhigh Subjects.The Journal of clinical endocrinology and metabolism · 2025Article
- E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells.Genes & development · 2025Article
110 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The peptide hormone urocortin3 (Ucn3) is abundantly expressed by mature beta cells, yet its physiological role is unknown. Here we demonstrate that Ucn3 is stored and co-released with insulin and potentiates glucose-stimulated somatostatin secretion via cognate receptors on delta cells. Further, we found that islets lacking endogenous Ucn3 have fewer delta cells, reduced somatostatin content, impaired somatostatin secretion, and exaggerated insulin release, and that these defects are rectified by treatment with synthetic Ucn3 in vitro. Our observations indicate that the paracrine actions of Ucn3 activate a negative feedback loop that promotes somatostatin release to ensure the timely reduction of insulin secretion upon normalization of plasma glucose. Moreover, Ucn3 is markedly depleted from beta cells in mouse and macaque models of diabetes and in human diabetic islets. This suggests that Ucn3 is a key contributor to stable glycemic control, whose reduction during diabetes aggravates glycemic volatility and contributes to the pathophysiology of this disease.
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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.