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Functional Characte...
Functional Characterization of Native, High-Affinity GABAA Receptors in Human Pancreatic β Cells
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- Korol, Sergiy V (author)
- Uppsala universitet,Fysiologi,Molecular Physiology and Neuroscience
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- Jin, Zhe (author)
- Uppsala universitet,Fysiologi
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- Jin, Yang (author)
- Uppsala universitet,Fysiologi
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- Bhandage, Amol K., 1988- (author)
- Uppsala universitet,Fysiologi
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- Tengholm, Anders, 1971- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Gandasi, Nikhil R. (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Fysiologi
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- Barg, Sebastian, 1969- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Espes, Daniel, 1985- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Carlsson, Per-Ola (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Laver, Derek (author)
- University of Newcastle, Callaghan, Australia
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- Birnir, Bryndis (author)
- Uppsala universitet,Fysiologi,Molecular Physiology and Neuroscience
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- English.
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In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 30
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Annan medicin och hälsovetenskap -- Övrig annan medicin och hälsovetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Other Medical and Health Sciences -- Other Medical and Health Sciences not elsewhere specified (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- GABA
- GABA(A) receptor
- Pancreatic islet
- Type 2 diabetes
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Korol, Sergiy V
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Jin, Zhe
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Jin, Yang
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Bhandage, Amol K ...
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Tengholm, Anders ...
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Gandasi, Nikhil ...
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Barg, Sebastian, ...
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Espes, Daniel, 1 ...
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Carlsson, Per-Ol ...
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Laver, Derek
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Birnir, Bryndis
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Other Medical an ...
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and Other Medical an ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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EBioMedicine
- By the university
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Uppsala University