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 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.
journal_name
EBioMedicinejournal_title
EBioMedicineauthors
Korol SV,Jin Z,Jin Y,Bhandage AK,Tengholm A,Gandasi NR,Barg S,Espes D,Carlsson PO,Laver D,Birnir Bdoi
10.1016/j.ebiom.2018.03.014subject
Has Abstractpub_date
2018-04-01 00:00:00pages
273-282issn
2352-3964pii
S2352-3964(18)30098-7journal_volume
30pub_type
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