ArticleProceedings of the National Academy of Sciences of the United States of America2004
Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers.
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Who cites it
174 citing papers in PubMed, 445 citations in OpenAlex.
- Modulation of Pancreatic Activity by Ghrelin and Its Potential Effects on Acute Pancreatitis.Digestive diseases and sciences · 2026Review
- Human NKX2.2 influences islet endocrine cell fate choices through regulation of WNT pathway genes.bioRxiv : the preprint server for biology · 2025Article
- Review
- A perfect islet: reviewing recent protocol developments and proposing strategies for stem cell derived functional pancreatic islets.Stem cell research & therapy · 2025Review
- Review
- A novel stop-loss mutation in NKX2-2 gene as a cause of neonatal diabetes mellitus: molecular characterization and structural analysis.Acta diabetologica · 2024Article
- Ghrelin deletion and conditional ghrelin cell ablation increase pancreatic islet size in mice.The Journal of clinical investigation · 2023Article
- Major β cell-specific functions of NKX2.2 are mediated via the NK2-specific domain.Genes & development · 2023Article
- Differential use of the Nkx2.2 NK2 domain in developing pancreatic islets and neurons.Genes & development · 2023Review
- Pax4-Ghrelin mediates the conversion of pancreatic ε-cells to β-cells after extreme β-cell loss in zebrafish.Development (Cambridge, England) · 2023Article
- Review
- Pancreatic β-Cell Development and Regeneration.Cold Spring Harbor perspectives in biology · 2022Review
- Review
- Mechanistic Investigation of GHS-R Mediated Glucose-Stimulated Insulin Secretion in Pancreatic Islets.Biomolecules · 2022Article
- Interorgan crosstalk in pancreatic islet function and pathology.FEBS letters · 2022Review
- Conversion of Gastrointestinal Somatostatin-Expressing D Cells Into Insulin-Producing Beta-Like Cells UponFrontiers in endocrinology · 2022Article
- Article
- High Coexpression of the Ghrelin and LEAP2 Receptor GHSR With Pancreatic Polypeptide in Mouse and Human Islets.Endocrinology · 2021Article
- Ghrelin Based Therapy of Metabolic Diseases.Current medicinal chemistry · 2021Review
- Pancreas is a preeminent source of ghrelin after sleeve gastrectomy in Wistar rats.Histology and histopathology · 2020Article
114 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The pancreatic islet is necessary for maintaining glucose homeostasis. Within the pancreatic islet, the homeodomain protein Nkx2.2 is essential for the differentiation of all insulin-producing beta cells and a subset of glucagon-producing alpha cells (1). Mice lacking Nkx2.2 have relatively normal sized islets, but a large number of cells within the mutant islet fail to produce any of the four major islet hormones. In this study we demonstrate that Nkx2.2 mutant endocrine cells have been replaced by cells that produce ghrelin, an appetite-promoting peptide predominantly found in the stomach. Intriguingly, normal mouse pancreas also contains a small population of ghrelin-producing cells, defining a new islet "epsilon" cell population. The expansion of ghrelin-producing cells at the expense of beta cells may be a general phenomenon, because we demonstrate that Pax4 mutant mice display a similar phenotype. We propose that insulin and ghrelin cells share a common progenitor and that Nkx2.2 and Pax4 are required to specify or maintain differentiation of the beta cell fate. This finding also suggests that there is a genetic component underlying the balance between insulin and ghrelin in regulating glucose metabolism.
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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.