ArticleDiabetes2016
Inhibition of DYRK1A Stimulates Human β-Cell Proliferation.
Article in Diabetes, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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Who cites it
128 citing papers in PubMed, 209 citations in OpenAlex.
- Harmine selectively enhances human beta cell identity markers and function via protein kinase A pathways.Diabetologia · 2026Article
- The comparative cell physiology of stem cell-derived and primary human β cells.Nature reviews. Endocrinology · 2026Review
- Integrative Insights Into DYRK1A From Molecular Function to Therapeutic Advancement.Chemical biology & drug design · 2026Review
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
- A DYRK inhibitor ameliorates glucose homeostasis and increases incretin-producing cells in diabetic mice.Journal of molecular endocrinology · 2026Article
- Chicoric acid-rich extract ofFrontiers in pharmacology · 2026Article
- 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
- RSPO1, a potent inducer of pancreatic β cell neogenesis.Cell reports. Medicine · 2025Article
- Active targeting of type 1 diabetes therapies to pancreatic beta cells using nanocarriers.Diabetologia · 2025Review
- Anti-tumor potential of Harmine and its derivatives: recent trends and advancements.Discover oncology · 2025Review
- SPOCK2 controls the proliferation and function of immature pancreatic β-cells through MMP2.Experimental & molecular medicine · 2025Article
- Promotion of beta cell proliferation through DYRK kinase inhibition using the marine natural product breitfussin C.Scientific reports · 2025Article
- A novel dual DYRK1A/B inhibitor for the treatment of type 1 diabetes.Frontiers in pharmacology · 2025Article
- 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
- Harmine exhibits anti-apoptotic properties and reduces diabetes-induced testicular damage caused by streptozotocin in rats.Clinical and experimental reproductive medicine · 2024Article
- Inactivation of HIPK2 attenuates KRASJournal of experimental & clinical cancer research : CR · 2024Article
- Intestinal Nogo-B reduces GLP1 levels by binding to proglucagon on the endoplasmic reticulum to inhibit PCSK1 cleavage.Nature communications · 2024Article
- β-cell neogenesis: A rising star to rescue diabetes mellitus.Journal of advanced research · 2024Review
68 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Restoring functional β-cell mass is an important therapeutic goal for both type 1 and type 2 diabetes (1). While proliferation of existing β-cells is the primary means of β-cell replacement in rodents (2), it is unclear whether a similar principle applies to humans, as human β-cells are remarkably resistant to stimulation of division (3,4). Here, we show that 5-iodotubercidin (5-IT), an annotated adenosine kinase inhibitor previously reported to increase proliferation in rodent and porcine islets (5), strongly and selectively increases human β-cell proliferation in vitro and in vivo. Remarkably, 5-IT also increased glucose-dependent insulin secretion after prolonged treatment. Kinome profiling revealed 5-IT to be a potent and selective inhibitor of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) and cell division cycle-like kinase families. Induction of β-cell proliferation by either 5-IT or harmine, another natural product DYRK1A inhibitor, was suppressed by coincubation with the calcineurin inhibitor FK506, suggesting involvement of DYRK1A and nuclear factor of activated T cells signaling. Gene expression profiling in whole islets treated with 5-IT revealed induction of proliferation- and cell cycle-related genes, suggesting that true proliferation is induced by 5-IT. Furthermore, 5-IT promotes β-cell proliferation in human islets grafted under the kidney capsule of NOD-scid IL2Rg(null) mice. These results point to inhibition of DYRK1A as a therapeutic strategy to increase human β-cell proliferation.
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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.