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Cited by 117Pancreatic function and diabetesDiabetes Treatment and ManagementNeuroscience and Neuropharmacology Research

γ-Aminobutyric acid (GABA) signalling in human pancreatic islets is altered in type 2 diabetes

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Taneera, J., Jin, Z., Jin, Y., Muhammed, S. J., Zhang, E., Lang, S., Salehi, A., Korsgren, O. +3 more·2012·Diabetologia
DOI 10.1007/s00125-012-2548-7PMC PMC3369140
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Abstract

AIMS/HYPOTHESIS: γ-Aminobutyric acid (GABA) is a signalling molecule in the interstitial space in pancreatic islets. We examined the expression and function of the GABA signalling system components in human pancreatic islets from normoglycaemic and type 2 diabetic individuals. METHODS: Expression of GABA signalling system components was studied by microarray, quantitative PCR analysis, immunohistochemistry and patch-clamp experiments on cells in intact islets. Hormone release was measured from intact islets. RESULTS: The GABA signalling system was compromised in islets from type 2 diabetic individuals, where the expression of the genes encoding the α1, α2, β2 and β3 GABA(A) channel subunits was downregulated. GABA originating within the islets evoked tonic currents in the cells. The currents were enhanced by pentobarbital and inhibited by the GABA(A) receptor antagonist, SR95531. The effects of SR95531 on hormone release revealed that activation of GABA(A) channels (GABA(A) receptors) decreased both insulin and glucagon secretion. The GABA(B) receptor antagonist, CPG55845, increased insulin release in islets (16.7 mmol/l glucose) from normoglycaemic and type 2 diabetic individuals. CONCLUSIONS/INTERPRETATION: Interstitial GABA activates GABA(A) channels and GABA(B) receptors and effectively modulates hormone release in islets from type 2 diabetic and normoglycaemic individuals.

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  • GABAB antagonists such as CGP55485 stimulate insulin secretion in human islets.

    “GABAB antagonists such as CGP55485 stimulate insulin secretion in human islets (670).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [670]

    The Results (Fig. 5c) report that the GABAB antagonist CGP55845 increased insulin release in human islets at 16.7 mmol/l glucose, but not at 1 mmol/l. The claim gives a different compound number, CGP55485, and omits the high-glucose condition. (LLM, conf=0.90)

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  • In human islets, spontaneous activity of endogenous GABAA receptor Cl- channels is observed.

    “In human islets, spontaneous activity of endogenous GABAA receptor Cl- channels is observed (670), possibly reflecting the presence of an ambient GABA concentration sufficient to result in receptor activation.”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [670]

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Authors
Taneera, J., Jin, Z., Jin, Y., Muhammed, S. J., Zhang, E., Lang, S., Salehi, A., Korsgren, O., Renström, E., Groop, L., & Birnir, B.
Affiliations
  • Lund University (SE)
  • Uppsala University (SE)
Corresponding author
Birnir, B.
ORCID
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
2012-04-27
Volume
55
Issue
7
Pages
1985-1994
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/s00125-012-2548-7
PMC
PMC3369140
OpenAlex
W1977392097
Cited by
117
References
4
Citations by year
2026: 4 · 2025: 10 · 2024: 8 · 2023: 6 · 2022: 10 · 2021: 7 · 2020: 7 · 2019: 9 · 2018: 6 · 2017: 10 · 2016: 4 · 2015: 8 · 2014: 14 · 2013: 9 · 2012: 5
FWCI
11.21
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Diabetologia (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
Svenska Sällskapet för Medicinsk Forskning
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
GABA, GABA signalling, pancreatic islets, type 2 diabetes, GABAA receptor, GABAB receptors, insulin secretion, glucagon secretion, SR95531, pentobarbital
MeSH terms
Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Female, gamma-Aminobutyric Acid, Homeostasis, Humans, Immunohistochemistry, Male, Middle Aged, Pyridazines, Signal Transduction, Down-Regulation, Receptors, GABA-B, Disease Progression, GABA Antagonists, Insulin-Secreting Cells

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