ArticleCell metabolism2019
Combined Inhibition of DYRK1A, SMAD, and Trithorax Pathways Synergizes to Induce Robust Replication in Adult Human Beta Cells.
Article in Cell metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- Development and trend of stem cell therapy for diabetes: a comprehensive review based on knowledge visualization.Frontiers in immunology · 2026Pooled it
- Human and mouse regenerative macrophages enhance beta cell survival, function, and proliferation.Islets · 2026Article
- Inhibition of Dyrk1a attenuates type 1 diabetic cardiomyopathy via anti‑ferroptosis.Molecular medicine reports · 2026Article
- The comparative cell physiology of stem cell-derived and primary human β cells.Nature reviews. Endocrinology · 2026Review
- Type 2 diabetes mellitus.Nature reviews. Disease primers · 2026Review
- Genetic recording of pancreatic beta cell proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Naphthoquinones mediate differentiation of human umbilical cord derived mesenchymal stem cells into insulin producing cells through regulation of Wnt and BMP pathways.BioImpacts : BI · 2026Article
- The protein deacetylase SIRT2 exerts metabolic control over adaptive β cell proliferation.The Journal of clinical investigation · 2025Article
- Drug-induced regeneration of pancreatic beta cells: An approach to cellular therapeutic targets.Cell regeneration (London, England) · 2025Review
- SIRT5-modified human umbilical cord mesenchymal stem cells loaded with antioxidant polydopamine nanozyme enhance parpi resistance in ovarian cancer via fatty acid metabolism reprogramming.Journal of nanobiotechnology · 2025Article
- Chaperone-mediated autophagy directs a dual mechanism to balance premature senescence and senolysis to prevent intervertebral disc degeneration.Bone research · 2025Article
- Mechanistic insights and approaches for beta cell regeneration.Nature chemical biology · 2025Review
- DYRK1B phosphorylates FOXO1 to promote hepatic gluconeogenesis.Nucleic acids research · 2025Article
- SPOCK2 controls the proliferation and function of immature pancreatic β-cells through MMP2.Experimental & molecular medicine · 2025Article
- Type 2 Diabetes Mellitus: New Pathogenetic Mechanisms, Treatment and the Most Important Complications.International journal of molecular sciences · 2025Review
- Harnessing beta-cell replication: advancing molecular insights to regenerative therapies in diabetes.Frontiers in endocrinology · 2025Review
- Cycling alpha cells in regenerative drug-treated human pancreatic islets may serve as key beta cell progenitors.Cell reports. Medicine · 2024Article
- Engineered tools to study endocrine dysfunction of pancreas.Biophysics reviews · 2024Review
- Harmine and exendin-4 combination therapy safely expands human β cell mass in vivo in a mouse xenograft system.Science translational medicine · 2024Article
- Pancreatic beta-cell mass and function and therapeutic implications of using antidiabetic medications in type 2 diabetes.Journal of diabetes investigation · 2024Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
Abstract
Small-molecule inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) induce human beta cells to proliferate, generating a labeling index of 1.5%-3%. Here, we demonstrate that combined pharmacologic inhibition of DYRK1A and transforming growth factor beta superfamily (TGFβSF)/SMAD signaling generates remarkable further synergistic increases in human beta cell proliferation (average labeling index, 5%-8%, and as high as 15%-18%), and increases in both mouse and human beta cell numbers. This synergy reflects activation of cyclins and cdks by DYRK1A inhibition, accompanied by simultaneous reductions in key cell-cycle inhibitors (CDKN1C and CDKN1A). The latter results from interference with the basal Trithorax- and SMAD-mediated transactivation of CDKN1C and CDKN1A. Notably, combined DYRK1A and TGFβ inhibition allows preservation of beta cell differentiated function. These beneficial effects extend from normal human beta cells and stem cell-derived human beta cells to those from people with type 2 diabetes, and occur both in vitro and in vivo.
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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.