ArticleJCI insight2020
Pharmacologic and genetic approaches define human pancreatic β cell mitogenic targets of DYRK1A inhibitors.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- Harmine selectively enhances human beta cell identity markers and function via protein kinase A pathways.Diabetologia · 2026Article
- Phosphoproteomics identifies the DYRK1B protein kinase as a regulator of processing bodies.Journal of cell science · 2026Article
- Therapeutic Potential of GLP-1 Receptor Agonists in Diabetes and Cardiovascular Disease: Mechanisms and Clinical Implications.Cardiovascular drugs and therapy · 2026Review
- DYRK1A inhibition restores pancreatic functions and improves glucose metabolism in a preclinical model of type 2 diabetes.Molecular metabolism · 2025Article
- Drug-induced regeneration of pancreatic beta cells: An approach to cellular therapeutic targets.Cell regeneration (London, England) · 2025Review
- Mechanistic insights and approaches for beta cell regeneration.Nature chemical biology · 2025Review
- Discovery of a novel DYRK1A inhibitor with neuroprotective activity by virtual screening and in vitro biological evaluation.Molecular diversity · 2025Article
- SPOCK2 controls the proliferation and function of immature pancreatic β-cells through MMP2.Experimental & molecular medicine · 2025Article
- Cycling alpha cells in regenerative drug-treated human pancreatic islets may serve as key beta cell progenitors.Cell reports. Medicine · 2024Article
- Single cell multiome profiling of pancreatic islets reveals physiological changes in cell type-specific regulation associated with diabetes risk.bioRxiv : the preprint server for biology · 2024Article
- Harmine and exendin-4 combination therapy safely expands human β cell mass in vivo in a mouse xenograft system.Science translational medicine · 2024Article
- Targeting Protein Kinases to Protect Beta-Cell Function and Survival in Diabetes.International journal of molecular sciences · 2024Review
- Targeting the DYRK1A kinase prevents cancer progression and metastasis and promotes cancer cells response to G1/S targeting chemotherapy drugs.NPJ precision oncology · 2024Article
- Scaling Insulin-Producing Cells by Multiple Strategies.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- The dual-specificity kinase DYRK1A interacts with the Hepatitis B virus genome and regulates the production of viral RNA.PloS one · 2024Article
- Relieving DYRK1A repression of MKL1 confers an adult-like phenotype to human infantile megakaryocytes.The Journal of clinical investigation · 2022Article
- Disrupting the DREAM complex enables proliferation of adult human pancreatic β cells.The Journal of clinical investigation · 2022Article
- Small-molecule discovery in the pancreatic beta cell.Current opinion in chemical biology · 2022Review
- Inhibition of DYRK1a Enhances Cardiomyocyte Cycling After Myocardial Infarction.Circulation research · 2022Article
- Identification and analysis of a selective DYRK1A inhibitor.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Small molecule inhibitors of dual specificity, tyrosine phosphorylation-regulated kinase 1A (DYRK1A), including harmine and others, are able to drive human β cell regeneration. While DYRK1A is certainly a target of this class, whether it is the only or the most important target is uncertain. Here, we employ a combined pharmacologic and genetic approach to refine the potential mitogenic targets of the DYRK1A inhibitor family in human islets. A combination of human β cell RNA sequencing, DYRK1A inhibitor kinome screens, pharmacologic inhibitors, and targeted silencing of candidate genes confirms that DYRK1A is a central target. Surprisingly, however, DYRK1B also proves to be an important target: silencing DYRK1A results in an increase in DYRK1B. Simultaneous silencing of both DYRK1A and DYRK1B yields greater β cell proliferation than silencing either individually. Importantly, other potential kinases, such as the CLK and the GSK3 families, are excluded as important harmine targets. Finally, we describe adenoviruses that are able to silence up to 7 targets simultaneously. Collectively, we report that inhibition of both DYRK1A and DYRK1B is required for induction of maximal rates of human β cell proliferation, and we provide clarity for future efforts in structure-based drug design for human β cell regenerative drugs.
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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.