ArticleProceedings of the National Academy of Sciences of the United States of America2015
CK2 acts as a potent negative regulator of receptor-mediated insulin release in vitro and in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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
25 citing papers in PubMed, 30 citations in OpenAlex.
- Contribution of parasympathetic muscarinic augmentation of insulin secretion to olanzapine-induced hyperinsulinemia.American journal of physiology. Endocrinology and metabolism · 2018Trial
- Microglial protein kinase CK2 prevents obesity in mice potentially through NLRP3 inflammasome activation.Nature communications · 2026Article
- ENaC phosphorylation facilitates ankyrin-3 interaction critical for renal sodium balance.PNAS nexus · 2026Article
- Protective effect of CK2 against endoplasmic reticulum stress in pancreatic β cells.Diabetology international · 2025Article
- CK2 activity is crucial for proper glucagon expression.Diabetologia · 2024Article
- Review
- GPCRs in Intracellular Compartments: New Targets for Drug Discovery.Biomolecules · 2022Review
- The Role of Protein Kinase CK2 in Development and Disease Progression: A Critical Review.Journal of developmental biology · 2022Review
- SGC-CK2-1 Is an Efficient Inducer of Insulin Production and Secretion in Pancreatic β-Cells.Pharmaceutics · 2021Article
- β-Arrestin-1 is required for adaptive β-cell mass expansion during obesity.Nature communications · 2021Article
- Protein kinase CK2: a potential therapeutic target for diverse human diseases.Signal transduction and targeted therapy · 2021Review
- Pyrvinium Treatment Confers Hepatic Metabolic Benefits via β-Catenin Downregulation and AMPK Activation.Pharmaceutics · 2021Article
- Protein Kinase CK2 Controls CaInternational journal of molecular sciences · 2020Article
- Effects of Casein Kinase 2 Alpha 1 Gene Expression on Mice Liver Susceptible to Type 2 Diabetes Mellitus and Obesity.International journal of medical sciences · 2020Article
- Protein Kinase CK2-A Putative Target for the Therapy of Diabetes Mellitus?International journal of molecular sciences · 2019Review
- Uterine GαFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Triazole-Based Inhibitors of the Wnt/β-Catenin Signaling Pathway Improve Glucose and Lipid Metabolisms in Diet-Induced Obese Mice.Journal of medicinal chemistry · 2019Article
- Hepatic Gi signaling regulates whole-body glucose homeostasis.The Journal of clinical investigation · 2018Article
- The importance of negative determinants as modulators of CK2 targeting. The lesson of Akt2 S131.PloS one · 2018Article
- CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
G protein-coupled receptors (GPCRs) regulate virtually all physiological functions including the release of insulin from pancreatic β-cells. β-Cell M3 muscarinic receptors (M3Rs) are known to play an essential role in facilitating insulin release and maintaining proper whole-body glucose homeostasis. As is the case with other GPCRs, M3R activity is regulated by phosphorylation by various kinases, including GPCR kinases and casein kinase 2 (CK2). At present, it remains unknown which of these various kinases are physiologically relevant for the regulation of β-cell activity. In the present study, we demonstrate that inhibition of CK2 in pancreatic β-cells, knockdown of CK2α expression, or genetic deletion of CK2α in β-cells of mutant mice selectively augmented M3R-stimulated insulin release in vitro and in vivo. In vitro studies showed that this effect was associated with an M3R-mediated increase in intracellular calcium levels. Treatment of mouse pancreatic islets with CX4945, a highly selective CK2 inhibitor, greatly reduced agonist-induced phosphorylation of β-cell M3Rs, indicative of CK2-mediated M3R phosphorylation. We also showed that inhibition of CK2 greatly enhanced M3R-stimulated insulin secretion in human islets. Finally, CX4945 treatment protected mice against diet-induced hyperglycemia and glucose intolerance in an M3R-dependent fashion. Our data demonstrate, for the first time to our knowledge, the physiological relevance of CK2 phosphorylation of a GPCR and suggest the novel concept that kinases acting on β-cell GPCRs may represent novel therapeutic targets.
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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.