ArticleNature metabolism2019
Mechanism and effects of pulsatile GABA secretion from cytosolic pools in the human beta cell.
Article in Nature metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
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Who cites it
69 citing papers in PubMed, 106 citations in OpenAlex.
- The intracellular subdomain of the volume-regulated anion channel subunit LRRC8A is a hotspot of channel activation.Nature communications · 2026Article
- Peripheral GABA Signaling in Metabolic Adaptation and Maladaptation.International journal of molecular sciences · 2026Review
- Supplementation of γ-Aminobutyric Acid as a Functional Nutrient.Nutrients · 2026Review
- GABA Regulates CaMetabolites · 2026Article
- Microglial SWELL1 deficiency drives male-specific seizure vulnerability but paradoxical neuroprotection through impaired phagocytosis.JCI insight · 2026Article
- LRRC8A: A multifaceted regulator in cancer, neurological disorders, metabolic diseases and immune modulation.Genes & diseases · 2026Review
- The Dual Anaplerotic Model (DAM): Integral Roles of Pyruvate Carboxylase and the GABA Shunt in Beta Cell Insulin Secretion.Life (Basel, Switzerland) · 2026Article
- Puromycin-sensitive aminopeptidase acts as an inhibitory auxiliary subunit of volume-regulated anion channels and regulates cGAMP transport.Molecular cell · 2025Article
- Beta cell secreted GABA sets appropriate insulin secretion by modulating islet calcium oscillations.Molecular metabolism · 2025Article
- LRRC8A in endothelial cells contributes to the aberrant blood-brain barrier integrity in ischaemic stroke.Stroke and vascular neurology · 2025Article
- LRRC8 complexes are ATP release channels that regulate platelet activation and arterial thrombosis.Blood · 2025Article
- Puromycin-sensitive aminopeptidase acts as an inhibitory auxiliary subunit of volume-regulated anion channels.bioRxiv : the preprint server for biology · 2025Article
- Article
- LRRC8 channel complexes counterbalance KATP channels to mediate swell-secretion coupling in mouse pancreatic β cells.JCI insight · 2025Article
- Re-evaluating Intra-Islet Paracrine Signaling: Precision, Pulsatility and the Path toward Mechanistic Clarity.Journal of biomedical research & environmental sciences · 2025Article
- Microglial SWELL1 Deficiency Drives Male-Specific Seizure Vulnerability but Paradoxical Neuroprotection through Impaired Phagocytosis.bioRxiv : the preprint server for biology · 2025Article
- Targeting GABA signaling in type 1 diabetes and its complications- an update on the state of the art.Pharmacological reports : PR · 2025Review
- GABA and GLP-1 receptor agonist combination therapy modifies diabetes and Langerhans islet cytoarchitecture in a rat model of Wolfram syndrome.Diabetology & metabolic syndrome · 2025Article
- Disease-modifying pharmacological treatments of type 1 diabetes: Molecular mechanisms, target checkpoints, and possible combinatorial treatments.Pharmacological reviews · 2025Review
- Recent insights on the impact of SWELL1 on metabolic syndromes.Frontiers in pharmacology · 2025Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 10 institutions in 6 countries.
Funding
Abstract
Pancreatic beta cells synthesize and secrete the neurotransmitter γ-aminobutyric acid (GABA) as a paracrine and autocrine signal to help regulate hormone secretion and islet homeostasis. Islet GABA release has classically been described as a secretory vesicle-mediated event. Yet, a limitation of the hypothesized vesicular GABA release from islets is the lack of expression of a vesicular GABA transporter in beta cells. Consequentially, GABA accumulates in the cytosol. Here we provide evidence that the human beta cell effluxes GABA from a cytosolic pool in a pulsatile manner, imposing a synchronizing rhythm on pulsatile insulin secretion. The volume regulatory anion channel (VRAC), functionally encoded by LRRC8A or Swell1, is critical for pulsatile GABA secretion. GABA content in beta cells is depleted and secretion is disrupted in islets from type 1 and type 2 diabetic patients, suggesting that loss of GABA as a synchronizing signal for hormone output may correlate with diabetes pathogenesis.
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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.