- Title
- Functional characterization of native, high-affinity GABAA receptors in human pancreatic ß cells
- Creator
- Korol, Sergiy V.; Jin, Zhe; Birnir, Bryndis; Jin, Yang; Bhandage, Amol K.; Tengholm, Anders; Gandasi, Nikhil R.; Barg, Sebastian; Espes, Daniel; Carlsson, Per-Ola; Laver, Derek
- Relation
- EBioMedicine Vol. 30, Issue April 2018, p. 273-282
- Publisher Link
- http://dx.doi.org/10.1016/j.ebiom.2018.03.014
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2018
- Description
- 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 GABAA receptors in human islet β cells as biological sensors and reveal that 100–1000 nM 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. GABAA 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 GABAA receptors signaling in human islets β cells that is GABA concentration-dependent, differentially regulated by drugs, modulates insulin secretion and is altered in T2D.
- Subject
- GABA; GABAA receptor; pancreatic islet; type 2 diabetes
- Identifier
- http://hdl.handle.net/1959.13/1384251
- Identifier
- uon:32032
- Identifier
- ISSN:2352-3964
- Rights
- © 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
- Language
- eng
- Full Text
- Reviewed
- Hits: 6333
- Visitors: 6811
- Downloads: 332
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 2 MB | Adobe Acrobat PDF | View Details Download |