ArticleEndocrinology2014
Pancreatic β-cell-specific ablation of TASK-1 channels augments glucose-stimulated calcium entry and insulin secretion, improving glucose tolerance.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
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- Molecular mechanism responsible for sex differences in electrical activity of mouse pancreatic β cells.JCI insight · 2024Article
- Investigation of Pancreatic-beta Cells Role in the Biological Process of Ageing.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets.Molecules (Basel, Switzerland) · 2022Review
- Regulation of α-cell glucagon secretion: The role of second messengers.Chronic diseases and translational medicine · 2022Review
- Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels.Current neuropharmacology · 2022Review
- pH-Dependence of Glucose-Dependent Activity of Beta Cell Networks in Acute Mouse Pancreatic Tissue Slice.Frontiers in endocrinology · 2022Article
- Transcriptional changes and the role of ONECUT1 in hPSC pancreatic differentiation.Communications biology · 2021Article
- Beta-Cell Ion Channels and Their Role in Regulating Insulin Secretion.Comprehensive Physiology · 2021Review
- KCNK3 Mutation Causes Altered Immune Function in Pulmonary Arterial Hypertension Patients and Mouse Models.International journal of molecular sciences · 2021Article
- Postnatal maturation of calcium signaling in islets of Langerhans from neonatal mice.Cell calcium · 2021Article
- TASK-1 and TASK-3 channels modulate pressure overload-induced cardiac remodeling and dysfunction.American journal of physiology. Heart and circulatory physiology · 2020Article
- Islet-Like Structures Generated In Vitro from Adult Human Liver Stem Cells Revert Hyperglycemia in Diabetic SCID Mice.Stem cell reviews and reports · 2019Article
- Article
- Role of TREK-1 in Health and Disease, Focus on the Central Nervous System.Frontiers in pharmacology · 2019Review
- Article
- SWELL1 is a glucose sensor regulating β-cell excitability and systemic glycaemia.Nature communications · 2018Article
- Simultaneous Real-Time Measurement of the β-Cell Membrane Potential and CaMethods in molecular biology (Clifton, N.J.) · 2018Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
Calcium entry through voltage-dependent Ca(2+) channels (VDCCs) is required for pancreatic β-cell insulin secretion. The 2-pore-domain acid-sensitive potassium channel (TASK-1) regulates neuronal excitability and VDCC activation by hyperpolarizing the plasma membrane potential (Δψp); however, a role for pancreatic β-cell TASK-1 channels is unknown. Here we examined the influence of TASK-1 channel activity on the β-cell Δψp and insulin secretion during secretagogue stimulation. TASK-1 channels were found to be highly expressed in human and rodent islets and localized to the plasma membrane of β-cells. TASK-1-like currents of mouse and human β-cells were blocked by the potent TASK-1 channel inhibitor, A1899 (250nM). Although inhibition of TASK-1 currents did not influence the β-cell Δψp in the presence of low (2mM) glucose, A1899 significantly enhanced glucose-stimulated (14mM) Δψp depolarization of human and mouse β-cells. TASK-1 inhibition also resulted in greater secretagogue-stimulated Ca(2+) influx in both human and mouse islets. Moreover, conditional ablation of mouse β-cell TASK-1 channels reduced K2P currents, increased glucose-stimulated Δψp depolarization, and augmented secretagogue-stimulated Ca(2+) influx. The Δψp depolarization caused by TASK-1 inhibition resulted in a transient increase in glucose-stimulated mouse β-cell action potential (AP) firing frequency. However, secretagogue-stimulated β-cell AP duration eventually increased in the presence of A1899 as well as in β-cells without TASK-1, causing a decrease in AP firing frequency. Ablation or inhibition of mouse β-cell TASK-1 channels also significantly enhanced glucose-stimulated insulin secretion, which improved glucose tolerance. Conversely, TASK-1 ablation did not perturb β-cell Δψp, Ca(2+) influx, or insulin secretion under low-glucose conditions (2mM). These results reveal a glucose-dependent role for β-cell TASK-1 channels of limiting glucose-stimulated Δψp depolarization and insulin secretion, which modulates glucose homeostasis.
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