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Cited by 289Neuroscience and Neuropharmacology ResearchTryptophan and brain disordersVagus Nerve Stimulation Research

GABA is an effective immunomodulatory molecule

Open access
Jin, Zhe, Mendu, Suresh Kumar, Birnir, Bryndis·2013·Amino Acids
DOI 10.1007/s00726-011-1193-7PMC PMC3680704
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Abstract

In recent years, it has become clear that there is an extensive cross-talk between the nervous and the immune system. Somewhat surprisingly, the immune cells themselves do express components of the neuronal neurotransmitters systems. What role the neurotransmitters, their ion channels, receptors and transporters have in immune function and regulation is an emerging field of study. Several recent studies have shown that the immune system is capable of synthesizing and releasing the classical neurotransmitter GABA (γ-aminobutyric acid). GABA has a number of effects on the immune cells such as activation or suppression of cytokine secretion, modification of cell proliferation and GABA can even affect migration of the cells. The immune cells encounter GABA when released by the immune cells themselves or when the immune cells enter the brain. In addition, GABA can also be found in tissues like the lymph nodes, the islets of Langerhans and GABA is in high enough concentration in blood to activate, e.g., GABA-A channels. GABA appears to have a role in autoimmune diseases like multiple sclerosis, type 1 diabetes, and rheumatoid arthritis and may modulate the immune response to infections. In the near future, it will be important to work out what specific effects GABA has on the function of the different types of immune cells and determine the underlying mechanisms. In this review, we discuss some of the recent findings revealing the role of GABA as an immunomodulator.

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  • Activation of GABA receptors leads to Ca2+-influx stimulating or activation of PI3K/Akt/PKB pathway resulting in increased insulin release, promotes pancreatic β-cell proliferation, and inhibits apoptosis.

    “Pancreas β-cells express gamma amino butyric acid receptor A/B (GABAA/BRs) and activation of GABA receptors leads to Ca2+-influx stimulating or activation of PI3K/Akt/PKB pathway resulting in increased insulin release promotes pancreatic β-cells proliferation and inhibits apoptosis.”

    From A critical review on diabetes mellitus type 1 and type 2 management approaches: from lifestyle modification to current and novel targets and therapeutic agents. (2024) · cites this paper as [102]

    The References (page unavailable) list a study titled “GABA exerts protective and regenerative effects on islet beta cells,” which supports the claim’s broad point about β-cell protection and regeneration. But this paper does not state that β-cell GABA-receptor activation increases insulin release, promotes proliferation or inhibits apoptosis through Ca2+ influx or PI3K/Akt/PKB. Its Conclusion (page unavailable) discusses possible calcium entry in immune cells, not β-cells. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • GABA regulates both the survival and regeneration of human pancreatic β-cells.

    “Thus, GABA regulates both the survival and regeneration of human pancreatic β-cells.”

    From A critical review on diabetes mellitus type 1 and type 2 management approaches: from lifestyle modification to current and novel targets and therapeutic agents. (2024) · cites this paper as [102]

    The References (page unavailable) list a study titled “GABA exerts protective and regenerative effects on islet beta cells,” which supports the general survival-and-regeneration point. The cited paper’s own text does not establish those effects specifically in human pancreatic β-cells; its Introduction (page unavailable) says only that GABA is present in the pancreas and pancreatic islets. (LLM, conf=0.78)

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Cited by

Sorted by citations

Authors
Jin, Z., Mendu, S. K., & Birnir, B.
Affiliations
Uppsala University (SE)
Corresponding author
Birnir, Bryndis
ORCID
Venue
Amino Acids
Publisher
Springer Science and Business Media LLC
Published
2011-12-13
Volume
45
Issue
1
Pages
87-94
ISSN
  • 0939-4451 (ISSN-L)
  • 1438-2199
DOI
10.1007/s00726-011-1193-7
PMC
PMC3680704
OpenAlex
W1964841183
Cited by
289
References
2
Citations by year
2026: 13 · 2025: 28 · 2024: 24 · 2023: 30 · 2022: 30 · 2021: 26 · 2020: 24 · 2019: 21 · 2018: 16 · 2017: 20 · 2016: 19 · 2015: 13 · 2014: 17 · 2013: 5 · 2012: 3
FWCI
0.76
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Amino Acids (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Svenska Sällskapet för Medicinsk Forskning
  • Vetenskapsrådet
  • Uppsala Universitet
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Keywords
GABA, immunomodulation, neuroimmune interactions, GABAA receptor, cytokine production, immune cell proliferation, leukocyte migration, autoimmune disease, multiple sclerosis, type 1 diabetes, rheumatoid arthritis, infection immunity, lymph nodes, pancreatic islets
MeSH terms
Animals, Arthritis, Rheumatoid, Diabetes Mellitus, Type 1, gamma-Aminobutyric Acid, Humans, Multiple Sclerosis, T-Lymphocytes, Neuroimmunomodulation, Signal Transduction, Receptors, GABA, Mice

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