ArticleDevelopment (Cambridge, England)2015
Glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis.
Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 140 citations in OpenAlex.
- Enteroendocrine cells wire the gut-brain vagal axis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Markers of beta cell and alpha cell mass in human stem cell-generated implants with glycemic control at human setpoint.Stem cells translational medicine · 2026Article
- Streptozotocin induced hyperglycemia in the axolotl.Developmental dynamics : an official publication of the American Association of Anatomists · 2026Article
- Zebrafish as an effective model for accelerating diabetes research from discovery to therapy.Journal of diabetes and metabolic disorders · 2025Review
- Identification of intestinal enteroendocrine cell subtypes and their associated hormones in zebrafish.PLoS biology · 2025Article
- Mechanistic insights and approaches for beta cell regeneration.Nature chemical biology · 2025Review
- Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners.Molecular metabolism · 2024Article
- Examining the liver-pancreas crosstalk reveals a role for the molybdenum cofactor in β-cell regeneration.Life science alliance · 2024Article
- Alpha- to Beta-Cell Transdifferentiation in Neonatal Compared with Adult Mouse Pancreas in Response to a Modest Reduction in Beta-Cells Using Streptozotocin.International journal of molecular sciences · 2024Article
- Negative cell cycle regulation by calcineurin is necessary for proper beta cell regeneration in zebrafish.eLife · 2024Article
- Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners.bioRxiv : the preprint server for biology · 2024Article
- Transdifferentiation is temporally uncoupled from progenitor pool expansion during hair cell regeneration in the zebrafish inner ear.Development (Cambridge, England) · 2024Article
- Transdifferentiation is uncoupled from progenitor pool expansion during hair cell regeneration in the zebrafish inner ear.bioRxiv : the preprint server for biology · 2024Article
- Animal Models for Understanding the Mechanisms of Beta Cell Death during Type 2 Diabetes Pathogenesis.Biomedicines · 2024Review
- Single-Cell Sequencing Data Analysis Unveiled HDAC1 as the Therapeutic Target for Chronic Pancreatitis.Molecular biotechnology · 2024Article
- β-Cell Heterogeneity and Plasticity.Advances in anatomy, embryology, and cell biology · 2024Review
- Zebrafish pancreatic β cell clusters undergo stepwise regeneration using Neurod1-expressing cells from different cell lineages.Cell and tissue research · 2023Article
- Decoding pancreatic endocrine cell differentiation and β cell regeneration in zebrafish.Science advances · 2023Article
- An inducible model of chronic hyperglycemia.Disease models & mechanisms · 2023Article
- Glucagon Acting at the GLP-1 Receptor Contributes to β-Cell Regeneration Induced by Glucagon Receptor Antagonism in Diabetic Mice.Diabetes · 2023Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The interconversion of cell lineages via transdifferentiation is an adaptive mode of tissue regeneration and an appealing therapeutic target. However, its clinical exploitation is contingent upon the discovery of contextual regulators of cell fate acquisition and maintenance. In murine models of diabetes, glucagon-secreting alpha cells transdifferentiate into insulin-secreting beta cells following targeted beta cell depletion, regenerating the form and function of the pancreatic islet. However, the molecular triggers of this mode of regeneration are unknown. Here, using lineage-tracing assays in a transgenic zebrafish model of beta cell ablation, we demonstrate conserved plasticity of alpha cells during islet regeneration. In addition, we show that glucagon expression is upregulated after injury. Through gene knockdown and rescue approaches, we also find that peptides derived from the glucagon gene are necessary for alpha-to-beta cell fate switching. Importantly, whereas beta cell neogenesis was stimulated by glucose, alpha-to-beta cell conversion was not, suggesting that transdifferentiation is not mediated by glucagon/GLP-1 control of hepatic glucose production. Overall, this study supports the hypothesis that alpha cells are an endogenous reservoir of potential new beta cells. It further reveals that glucagon plays an important role in maintaining endocrine cell homeostasis through feedback mechanisms that govern cell fate stability.
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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.