ArticleProceedings of the National Academy of Sciences of the United States of America2010
ATP-gated P2X3 receptors constitute a positive autocrine signal for insulin release in the human pancreatic beta cell.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 129 citations in OpenAlex.
- Influence of hyperinsulinemia and insulin resistance on in vivo β-cell function: their role in human β-cell dysfunction.Diabetes · 2011Trial
- Article
- Re-evaluating Intra-Islet Paracrine Signaling: Precision, Pulsatility and the Path toward Mechanistic Clarity.Journal of biomedical research & environmental sciences · 2025Article
- FFAR4-mediated IL-6 release from islet macrophages promotes insulin secretion and is compromised in type-2 diabetes.Nature communications · 2025Article
- Pharmacology of P2X Receptors and Their Possible Therapeutic Potential in Obesity and Diabetes.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Extracellular electrophysiology on clonal human β-cell spheroids.Frontiers in endocrinology · 2024Article
- Metabolic and Molecular Amplification of Insulin Secretion.Advances in anatomy, embryology, and cell biology · 2024Review
- Article
- Pericyte dysfunction and impaired vasomotion are hallmarks of islets during the pathogenesis of type 1 diabetes.Cell reports · 2023Article
- Pancreatic β-cell heterogeneity in adult human islets and stem cell-derived islets.Cellular and molecular life sciences : CMLS · 2023Review
- A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling.Purinergic signalling · 2022Review
- Augmentation of Extracellular ATP Synergizes With Chemotherapy in Triple Negative Breast Cancer.Frontiers in oncology · 2022Article
- P2-type purinergic signaling in the regulation of pancreatic β-cell functional plasticity as a promising novel therapeutic approach for the treatment of type 2 diabetes?Frontiers in endocrinology · 2022Review
- ATP is an essential autocrine factor for pancreatic β-cell signaling and insulin secretion.Physiological reports · 2022Article
- ATP Secretion and Metabolism in Regulating Pancreatic Beta Cell Functions and Hepatic Glycolipid Metabolism.Frontiers in physiology · 2022Review
- Potential Therapeutic Targeting Neurotransmitter Receptors in Diabetes.Frontiers in endocrinology · 2022Review
- The Human Islet: Mini-Organ With Mega-Impact.Endocrine reviews · 2021Review
- Intercellular Communication in the Islet of Langerhans in Health and Disease.Comprehensive Physiology · 2021Article
- Purinergic signaling in diabetes and metabolism.Biochemical pharmacology · 2021Review
- Redox Homeostasis in Pancreatic β-Cells: From Development to Failure.Antioxidants (Basel, Switzerland) · 2021Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 1 institution in 2 countries.
Funding
Abstract
Extracellular ATP has been proposed as a paracrine signal in rodent islets, but it is unclear what role ATP plays in human islets. We now show the presence of an ATP signaling pathway that enhances the human beta cell's sensitivity and responsiveness to glucose fluctuations. By using in situ hybridization, RT-PCR, immunohistochemistry, and Western blotting as well as recordings of cytoplasmic-free Ca(2+) concentration, [Ca(2+)](i), and hormone release in vitro, we show that human beta cells express ionotropic ATP receptors of the P2X(3) type and that activation of these receptors by ATP coreleased with insulin amplifies glucose-induced insulin secretion. Released ATP activates P2X(3) receptors in the beta-cell plasma membrane, resulting in increased [Ca(2+)](i) and enhanced insulin secretion. Therefore, in human islets, released ATP forms a positive autocrine feedback loop that sensitizes the beta cell's secretory machinery. This may explain how the human pancreatic beta cell can respond so effectively to relatively modest changes in glucose concentration under physiological conditions in vivo.
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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.