ArticleThe Journal of clinical investigation2014
Targeting the cell cycle inhibitor p57Kip2 promotes adult human β cell replication.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Roles of Epigenetic Modifications in the Differentiation and Function of Pancreatic β-Cells.Frontiers in cell and developmental biology · 2020Pooled it
- High-Fat Diet-Fed Kcnq1 Mutant Mice Have Reduced Pancreatic β-Cell Mass via Gene-Environment Interaction.Diabetes & metabolism journal · 2026Article
- First In Vitro Human Islet Assessment of Oleanolic Acid (OA) and Its Serine Conjugate: Enhanced Solubility with Comparable Effects.Molecules (Basel, Switzerland) · 2025Article
- Identification of type 2 diabetes- and obesity-associated human β-cells using deep transfer learning.eLife · 2025Article
- Betagenin ameliorates diabetes by inducing insulin secretion and β-cell proliferation.The Journal of biological chemistry · 2025Article
- p57International journal of molecular sciences · 2024Article
- Article
- β cell regeneration and novel strategies for treatment of diabetes (Review).Biomedical reports · 2022Review
- Immunomodulator FTY720 improves glucose homeostasis and diabetic complications by rejuvenation of β-cell function in nonhuman primate model of diabetes.Fundamental & clinical pharmacology · 2022Article
- Copy number amplification-activated long non-coding RNA LINC00662 epigenetically inhibits BIK by interacting with EZH2 to regulate tumorigenesis in non-small cell lung cancer.Journal of Cancer · 2022Article
- Article
- Importance of Both Imprinted Genes and Functional Heterogeneity in Pancreatic Beta Cells: Is There a Link?International journal of molecular sciences · 2021Review
- DNA Methylation Patterning and the Regulation of Beta Cell Homeostasis.Frontiers in endocrinology · 2021Review
- Imprinted Genes Impact Upon Beta Cell Function in the Current (and Potentially Next) Generation.Frontiers in endocrinology · 2021Review
- Functional Versatility of the CDK Inhibitor p57Frontiers in cell and developmental biology · 2020Review
- Genomic imprinting and its effects on postnatal growth and adult metabolism.Cellular and molecular life sciences : CMLS · 2019Review
- Combined Inhibition of DYRK1A, SMAD, and Trithorax Pathways Synergizes to Induce Robust Replication in Adult Human Beta Cells.Cell metabolism · 2019Article
- Targeted demethylation at the CDKN1C/p57 locus induces human β cell replication.The Journal of clinical investigation · 2019Article
- Insulin mutations impair beta-cell development in a patient-derived iPSC model of neonatal diabetes.eLife · 2018Article
- Genetic and Epigenetic Control of CDKN1C Expression: Importance in Cell Commitment and Differentiation, Tissue Homeostasis and Human Diseases.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Children with focal hyperinsulinism of infancy display a dramatic, non-neoplastic clonal expansion of β cells that have undergone mitotic recombination, resulting in paternal disomy of part of chromosome 11. This disomic region contains imprinted genes, including the gene encoding the cell cycle inhibitor p57Kip2 (CDKN1C), which is silenced as a consequence of the recombination event. We hypothesized that targeting p57Kip2 could stimulate adult human β cell replication. Indeed, when we suppressed CDKN1C expression in human islets obtained from deceased adult organ donors and transplanted them into hyperglycemic, immunodeficient mice, β cell replication increased more than 3-fold. The newly replicated cells retained properties of mature β cells, including the expression of β cell markers such as insulin, PDX1, and NKX6.1. Importantly, these newly replicated cells demonstrated normal glucose-induced calcium influx, further indicating β cell functionality. These findings provide a molecular explanation for the massive β cell replication that occurs in children with focal hyperinsulinism. These data also provided evidence that β cells from older humans, in which baseline replication is negligible, can be coaxed to re-enter and complete the cell cycle while maintaining mature β cell properties. Thus, controlled manipulation of this pathway holds promise for the expansion of β cells in patients with type 2 diabetes.
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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.