ArticleScientific reports2018
Inhibition of TBK1/IKKε Promotes Regeneration of Pancreatic β-cells.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- A Framework for Selecting Zebrafish Models of Metabolic Diseases: Modeling Strategies, Phenotypic Validation, Mechanistic Investigation, and Efficacy Evaluation.Biomedicines · 2026Review
- Identification and verification of feature biomarkers associated with CD14Journal of diabetes investigation · 2025Article
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Article
- The Role of cGAS-STING Signalling in Metabolic Diseases: from Signalling Networks to Targeted Intervention.International journal of biological sciences · 2024Review
- Role of TBK1 Inhibition in Targeted Therapy of Cancer.Mini reviews in medicinal chemistry · 2024Review
- Article
- Identification and analysis of type 2 diabetes-mellitus-associated autophagy-related genes.Frontiers in endocrinology · 2023Article
- The role of TBK1 in cancer pathogenesis and anticancer immunity.Journal of experimental & clinical cancer research : CR · 2022Review
- Molecular study of the proliferation process of beta cells derived from pluripotent stem cells.Molecular biology reports · 2022Review
- Prediction of Drug Targets for Specific Diseases Leveraging Gene Perturbation Data: A Machine Learning Approach.Pharmaceutics · 2022Article
- Role of IKKε in the Metabolic Diseases: Physiology, Pathophysiology, and Pharmacology.Frontiers in pharmacology · 2022Review
- Diabetic Kinome Inhibitors-A New Opportunity for β-Cells Restoration.International journal of molecular sciences · 2021Review
- Zebra-Fishing for Regenerative Awakening in Mammals.Biomedicines · 2021Review
- Herbal Medicines Targeting the ImprovedEvidence-based complementary and alternative medicine : eCAM · 2021Review
- TBK1 regulates regeneration of pancreatic β-cells.Scientific reports · 2020Article
- Role of Phosphodiesterase in the Biology and Pathology of Diabetes.International journal of molecular sciences · 2020Review
- In vivo generation and regeneration of β cells in zebrafish.Cell regeneration (London, England) · 2020Review
- TBK1 regulates YAP/TAZ and fibrogenic fibroblast activation.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Pleiotropic roles of the insulin-like growth factor axis in type 1 diabetes.Current opinion in endocrinology, diabetes, and obesity · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
β-cell proliferation induction is a promising therapeutic strategy to restore β-cell mass. By screening small molecules in a transgenic zebrafish model of type 1 diabetes, we identified inhibitors of non-canonical IκB kinases (IKKs), TANK-binding kinase 1 (TBK1) and IκB kinase ε (IKKε), as enhancers of β-cell regeneration. The most potent β-cell regeneration enhancer was a cinnamic acid derivative (E)-3-(3-phenylbenzo[c]isoxazol-5-yl)acrylic acid (PIAA), which, acting through the cAMP-dependent protein kinase A (PKA), stimulated β-cell-specific proliferation by increasing cyclic AMP (cAMP) levels and mechanistic target of rapamycin (mTOR) activity. A combination of PIAA and cilostamide, an inhibitor of β-cell-enriched cAMP hydrolyzing enzyme phosphodiesterase (PDE) 3, enhanced β-cell proliferation, whereas overexpression of PDE3 blunted the mitogenic effect of PIAA in zebrafish. PIAA augmented proliferation of INS-1β-cells and β-cells in mammalian islets including human islets with elevation in cAMP levels and insulin secretion. PIAA improved glycemic control in streptozotocin (STZ)-induced diabetic mice with increases in β-cell proliferation, β-cell area, and insulin content in the pancreas. Collectively, these data reveal an evolutionarily conserved and critical role of TBK1/IKKε suppression in expanding functional β-cell mass.
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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.