ArticleScientific reports2020
TBK1 regulates regeneration of pancreatic β-cells.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
8 citing papers in PubMed, 9 citations in OpenAlex.
- Design and Synthesis of Novel Isoflavene TANK-Binding Kinase 1 Inhibitors With Anti-Inflammatory Activity.ChemMedChem · 2026Article
- Candidate genes related to growth and milk production in three Anatolian goats revealed by GWAS.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Endothelial FUNDC1 regulates metabolic reprogramming and the obesity-diabetes transition through the SIRT3/GATA2/endothelin-1 axis.Nature communications · 2026Article
- Omentin-1 as a promising biomarker and therapeutic target in hypertension and heart failure: a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- An INS-1 832/13 𝛽-Cell Proteome Highlights the Rapid Regulation of Fatty Acid Biosynthesis in Glucose-Stimulated Insulin Secretion.Proteomics · 2025Article
- Harnessing beta-cell replication: advancing molecular insights to regenerative therapies in diabetes.Frontiers in endocrinology · 2025Review
- Dysregulation of β-Cell Proliferation in Diabetes: Possibilities of Combination Therapy in the Development of a Comprehensive Treatment.Biomedicines · 2022Review
- Prediction of Drug Targets for Specific Diseases Leveraging Gene Perturbation Data: A Machine Learning Approach.Pharmaceutics · 2022Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
Abstract
Small-molecule inhibitors of non-canonical IκB kinases TANK-binding kinase 1 (TBK1) and IκB kinase ε (IKKε) have shown to stimulate β-cell regeneration in multiple species. Here we demonstrate that TBK1 is predominantly expressed in β-cells in mammalian islets. Proteomic and transcriptome analyses revealed that genetic silencing of TBK1 increased expression of proteins and genes essential for cell proliferation in INS-1 832/13 rat β-cells. Conversely, TBK1 overexpression decreased sensitivity of β-cells to the elevation of cyclic AMP (cAMP) levels and reduced proliferation of β-cells in a manner dependent on the activity of cAMP-hydrolyzing phosphodiesterase 3 (PDE3). While the mitogenic effect of (E)3-(3-phenylbenzo[c]isoxazol-5-yl)acrylic acid (PIAA) is derived from inhibition of TBK1, PIAA augmented glucose-stimulated insulin secretion (GSIS) and expression of β-cell differentiation and proliferation markers in human embryonic stem cell (hESC)-derived β-cells and human islets. TBK1 expression was increased in β-cells upon diabetogenic insults, including in human type 2 diabetic islets. PIAA enhanced expression of cell cycle control molecules and β-cell differentiation markers upon diabetogenic challenges, and accelerated restoration of functional β-cells in streptozotocin (STZ)-induced diabetic mice. Altogether, these data suggest the critical function of TBK1 as a β-cell autonomous replication barrier and present PIAA as a valid therapeutic strategy augmenting functional β-cells.
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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.