Functional Characterization of Native, High-Affinity GABA<sub>A</sub> Receptors in Human Pancreatic β Cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29606630.
- Also identified by DOI 10.1016/j.ebiom.2018.03.014 and PMC identifier 5952339.
- Licence recorded as CC BY-NC-ND.
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Abstract
In human pancreatic islets, the neurotransmitter γ-aminobutyric acid (GABA) is an extracellular signaling molecule synthesized by and released from the insulin-secreting β cells. The effective, physiological GABA concentration range within human islets is unknown. Here we use native GABA<sub>A</sub> receptors in human islet β cells as biological sensors and reveal that 100-1000nM GABA elicit the maximal opening frequency of the single-channels. In saturating GABA, the channels desensitized and stopped working. GABA modulated insulin exocytosis and glucose-stimulated insulin secretion. GABA<sub>A</sub> receptor currents were enhanced by the benzodiazepine diazepam, the anesthetic propofol and the incretin glucagon-like peptide-1 (GLP-1) but not affected by the hypnotic zolpidem. In type 2 diabetes (T2D) islets, single-channel analysis revealed higher GABA affinity of the receptors. The findings reveal unique GABA<sub>A</sub> receptors signaling in human islets β cells that is GABA concentration-dependent, differentially regulated by drugs, modulates insulin secretion and is altered in T2D.
Medical subject headings
- Insulin-Secreting Cells
- Receptors, GABA-A