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Functional Characterization of Native, High-Affinity GABAA Receptors in Human Pancreatic β Cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology. (Molecular Physiology and Neuroscience)ORCID iD: 0000-0001-8279-2790
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.ORCID iD: 0000-0002-4717-1558
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.ORCID iD: 0000-0002-7116-0939
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2018 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 30Article in journal (Refereed) Published
Abstract [en]

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 100-1000nM 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. 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.

Place, publisher, year, edition, pages
2018. Vol. 30
Keywords [en]
GABA, GABA(A) receptor, Pancreatic islet, Type 2 diabetes
National Category
Other Medical Sciences not elsewhere specified Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-348267DOI: 10.1016/j.ebiom.2018.03.014ISI: 000430303000032PubMedID: 29606630OAI: oai:DiVA.org:uu-348267DiVA, id: diva2:1196999
Funder
Swedish Research Council, 521-2009-4021EXODIAB - Excellence of Diabetes Research in SwedenSwedish Child Diabetes FoundationSwedish Diabetes AssociationNovo NordiskSwedish Society for Medical Research (SSMF)Swedish Research Council, 521-2012-1789Swedish Research Council, 2015-02417Swedish Research Council, 2017-00956Swedish Research Council, 2014-2575
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-06-19Bibliographically approved

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Korol, Sergiy VJin, ZheJin, YangBhandage, Amol K.Tengholm, AndersGandasi, Nikhil R.Barg, SebastianEspes, DanielCarlsson, Per-OlaBirnir, Bryndis

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Korol, Sergiy VJin, ZheJin, YangBhandage, Amol K.Tengholm, AndersGandasi, Nikhil R.Barg, SebastianEspes, DanielCarlsson, Per-OlaBirnir, Bryndis
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