ArticleScience translational medicine2020
GLP-1 receptor agonists synergize with DYRK1A inhibitors to potentiate functional human β cell regeneration.
Article in Science translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 119 citations in OpenAlex.
- Human and mouse regenerative macrophages enhance beta cell survival, function, and proliferation.Islets · 2026Article
- Harmine selectively enhances human beta cell identity markers and function via protein kinase A pathways.Diabetologia · 2026Article
- Integrative Insights Into DYRK1A From Molecular Function to Therapeutic Advancement.Chemical biology & drug design · 2026Review
- The Welander TIA1 mutation dedifferentiates insulin-producing cells: Reversal by a GLP-1 receptor agonist.The Journal of biological chemistry · 2026Article
- 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
- A DYRK inhibitor ameliorates glucose homeostasis and increases incretin-producing cells in diabetic mice.Journal of molecular endocrinology · 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
- Mechanistic insights and approaches for beta cell regeneration.Nature chemical biology · 2025Review
- DYRK1B phosphorylates FOXO1 to promote hepatic gluconeogenesis.Nucleic acids research · 2025Article
- Islet Cell Replacement and Regeneration for Type 1 Diabetes: Current Developments and Future Prospects.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Multi-omics approaches for biomarker discovery and precision diagnosis of prediabetes.Frontiers in endocrinology · 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
- Does Incretin Agonism Have Sustainable Efficacy?Cells · 2024Review
- Mechanistic Pathways and Clinical Implications of GLP-1 Receptor Agonists in Type 1 Diabetes Management.International journal of molecular sciences · 2024Review
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 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
6 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
Abstract
Glucagon-like peptide-1 receptor (GLP1R) agonists and dipeptidyl peptidase 4 inhibitors are widely prescribed diabetes drugs due to their ability to stimulate insulin secretion from remaining β cells and to reduce caloric intake. Unfortunately, they fail to increase human β cell proliferation. Small-molecule inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) are able to induce adult human β cell proliferation, but rates are modest (~2%), and their specificity to β cells is limited. Here, we provide evidence that combining any member of the GLP1R agonist class with any member of the DYRK1A inhibitor class induces a synergistic increase in human β cell replication (5 to 6%) accompanied by an actual increase in numbers of human β cells. GLP1R agonist-DYRK1A inhibitor synergy required combined inhibition of DYRK1A and an increase in cAMP and did not lead to β cell dedifferentiation. These beneficial effects on proliferation were seen in both normal human β cells and β cells derived from individuals with type 2 diabetes. The ability of the GLP1R agonist-DYRK1A inhibitor combination to enhance human β cell proliferation, human insulin secretion, and blood glucose control extended in vivo to studies of human islets transplanted into euglycemic and streptozotocin-diabetic immunodeficient mice. No adverse events were observed in the mouse studies during a 1-week period. Because of the relative β cell specificity of GLP1R agonists, the combination provides an improved, although not complete, degree of human β cell specificity.
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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.