Editing GABA (section)

=== Beyond the nervous system ===
[[File:Autoradiography of a brain slice from an embryonal rat - PMID19190758 PLoS 0004371.png|thumb|240px|mRNA expression of the embryonic variant of the GABA-producing enzyme [[GAD67]] in a coronal brain section of a one-day-old [[Laboratory rat#Wistar rat|Wistar rat]], with the highest expression in [[subventricular zone]] (svz)<ref name="pmid19190758">{{cite journal |vauthors=Popp A, Urbach A, Witte OW, Frahm C |title=Adult and embryonic GAD transcripts are spatiotemporally regulated during postnatal development in the rat brain |journal=[[PLoS ONE]] |volume=4 |issue=2 |pages=e4371 |year=2009 |pmid=19190758 |pmc=2629816|doi=10.1371/journal.pone.0004371 |editor1-last=Reh |editor1-first=Thomas A.|bibcode= 2009PLoSO...4.4371P|doi-access=free }}</ref>]]
Besides the nervous system, GABA is also produced at relatively high levels in the [[insulin]]-producing [[beta cell]]s (β-cells) of the [[pancreas]]. The β-cells secrete GABA along with insulin and the GABA binds to GABA receptors on the neighboring [[pancreatic islets|islet]] [[alpha cell]]s (α-cells) and inhibits them from secreting [[glucagon]] (which would counteract insulin's effects).<ref name="pmid2550826">{{cite journal |vauthors=Rorsman P, Berggren PO, Bokvist K, Ericson H, Möhler H, Ostenson CG, Smith PA |title=Glucose-inhibition of glucagon secretion involves activation of GABA<sub>A</sub>-receptor chloride channels |journal=Nature |volume=341 |issue=6239 |pages=233–6 |year=1989 |pmid=2550826 |doi=10.1038/341233a0 |bibcode=1989Natur.341..233R |s2cid=699135 }}</ref>

GABA can promote the replication and survival of β-cells<ref name="pmid21709230">{{cite journal |vauthors=Soltani N, Qiu H, Aleksic M, Glinka Y, Zhao F, Liu R, Li Y, Zhang N, Chakrabarti R, Ng T, Jin T, Zhang H, Lu WY, Feng ZP, Prud'homme GJ, Wang Q |title=GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=108 |issue=28 |pages=11692–7 |year=2011 |pmid=21709230 |pmc=3136292 |doi=10.1073/pnas.1102715108 |bibcode=2011PNAS..10811692S |doi-access=free }}</ref><ref name="pmid23995958">{{cite journal |vauthors=Tian J, Dang H, Chen Z, Guan A, Jin Y, Atkinson MA, Kaufman DL |title=γ-Aminobutyric acid regulates both the survival and replication of human β-cells |journal=Diabetes |volume=62 |issue=11 |pages=3760–5 |year=2013 |pmid=23995958 |pmc=3806626 |doi=10.2337/db13-0931 }}</ref><ref name="pmid25008178">{{cite journal |vauthors=Purwana I, Zheng J, Li X, Deurloo M, Son DO, Zhang Z, Liang C, Shen E, Tadkase A, Feng ZP, Li Y, Hasilo C, Paraskevas S, Bortell R, Greiner DL, Atkinson M, Prud'homme GJ, Wang Q |title=GABA promotes human β-cell proliferation and modulates glucose homeostasis |journal=Diabetes |volume=63 |issue=12 |pages=4197–205 |year=2014 |pmid=25008178 |doi=10.2337/db14-0153 |doi-access=free }}</ref> and also promote the conversion of α-cells to β-cells, which may lead to new treatments for [[diabetes]].<ref name="pmid27916274">{{cite journal |vauthors=Ben-Othman N, Vieira A, Courtney M, Record F, Gjernes E, Avolio F, Hadzic B, Druelle N, Napolitano T, Navarro-Sanz S, Silvano S, Al-Hasani K, Pfeifer A, Lacas-Gervais S, Leuckx G, Marroquí L, Thévenet J, Madsen OD, Eizirik DL, Heimberg H, Kerr-Conte J, Pattou F, Mansouri A, Collombat P |title=Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis |journal=Cell |volume=168 |issue=1–2 |pages=73–85.e11 |year=2017 |pmid=27916274 |doi=10.1016/j.cell.2016.11.002 |doi-access=free }}</ref>

Alongside GABAergic mechanisms, GABA has also been detected in other peripheral tissues including intestines, stomach, [[fallopian tubes]], [[uterus]], [[ovaries]], [[testicles]], [[kidneys]], [[urinary bladder]], the [[lungs]] and [[liver]], albeit at much lower levels than in neurons or β-cells.<ref name="pmid2405103">{{cite journal |vauthors= Erdö SL, Wolff JR |title= γ-Aminobutyric acid outside the mammalian brain |journal= J. Neurochem. |volume= 54 |issue= 2 |pages= 363–72 |date= February 1990 |pmid= 2405103 |doi= 10.1111/j.1471-4159.1990.tb01882.x|s2cid= 86144218 }}</ref>

Experiments on mice have shown that hypothyroidism induced by fluoride poisoning can be halted by administering GABA. The test also found that the thyroid recovered naturally without further assistance after the fluoride had been expelled by the GABA.<ref>{{cite journal | doi = 10.1016/j.lfs.2015.12.041 | volume=146 | title=γ-Aminobutyric acid ameliorates fluoride-induced hypothyroidism in male Kunming mice | year=2016 | journal=Life Sciences | pages=1–7 | vauthors=Yang H, Xing R, Liu S, Yu H, Li P | pmid=26724496 }}</ref>

[[Immune cell]]s express receptors for GABA<ref name="pmid10227421">{{cite journal |vauthors=Tian J, Chau C, Hales TG, Kaufman DL |title=GABA<sub>A</sub> receptors mediate inhibition of T cell responses |journal=J. Neuroimmunol. |volume=96 |issue=1 |pages=21–8 |year=1999 |pmid=10227421 |doi= 10.1016/s0165-5728(98)00264-1|s2cid=3006821 }}</ref><ref name="pmid22927941">{{cite journal |vauthors=Mendu SK, Bhandage A, Jin Z, Birnir B |title=Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes |journal=PLOS ONE |volume=7 |issue=8 |pages=e42959 |year=2012 |pmid=22927941 |pmc=3424250 |doi=10.1371/journal.pone.0042959 |bibcode=2012PLoSO...742959M |doi-access=free }}</ref> and administration of GABA can suppress [[inflammation|inflammatory]] immune responses and promote "regulatory" immune responses, such that GABA administration has been shown to inhibit [[autoimmune disease]]s in several animal models.<ref name="pmid21709230"/><ref name="pmid10227421"/><ref name="pmid15470076">{{cite journal |vauthors=Tian J, Lu Y, Zhang H, Chau CH, Dang HN, Kaufman DL |title=Gamma-aminobutyric acid inhibits T cell autoimmunity and the development of inflammatory responses in a mouse type 1 diabetes model |journal=J. Immunol. |volume=173 |issue=8 |pages=5298–304 |year=2004 |pmid=15470076 |doi= 10.4049/jimmunol.173.8.5298|doi-access=free }}</ref><ref name="pmid21604972">{{cite journal |vauthors=Tian J, Yong J, Dang H, Kaufman DL |title=Oral GABA treatment downregulates inflammatory responses in a mouse model of rheumatoid arthritis |journal=Autoimmunity |volume=44 |issue=6 |pages=465–70 |year=2011 |pmid=21604972 |pmc=5787624 |doi=10.3109/08916934.2011.571223 }}</ref>

In 2018, GABA was shown to regulate secretion of a greater number of cytokines. In plasma of [[T1D]] patients, levels of 26 [[cytokine]]s are increased and of those, 16 are inhibited by GABA in the cell assays.<ref>{{cite journal | vauthors = Bhandage AK, Jin Z, Korol SV, Shen Q, Pei Y, Deng Q, Espes D, Carlsson PO, Kamali-Moghaddam M, Birnir B | title = + T Cells and Is Immunosuppressive in Type 1 Diabetes | journal = eBioMedicine | volume = 30 | pages = 283–294 | date = April 2018 | pmid = 29627388 | pmc = 5952354 | doi = 10.1016/j.ebiom.2018.03.019 }}</ref>

In 2007, an excitatory GABAergic system was described in the airway [[epithelium]]. The system is activated by exposure to allergens and may participate in the mechanisms of [[asthma]].<ref name="GABA_lungs">{{cite journal |vauthors= Xiang YY, Wang S, Liu M, Hirota JA, Li J, Ju W, Fan Y, Kelly MM, Ye B, Orser B, O'Byrne PM, Inman MD, Yang X, Lu WY |title= A GABAergic system in airway epithelium is essential for mucus overproduction in asthma |journal= Nat. Med. |volume= 13 |issue= 7 |pages= 862–7 |date= July 2007 |pmid= 17589520 |doi= 10.1038/nm1604|s2cid= 2461757 }}</ref> GABAergic systems have also been found in the [[testis]]<ref name="Inyerballs">{{cite book |vauthors= Payne AH, Hardy MH |title=The Leydig cell in health and disease |publisher= Humana Press|year=2007 |isbn= 978-1-58829-754-9}}</ref> and in the eye lens.<ref name="GABA_lens">{{cite journal |vauthors= Kwakowsky A, Schwirtlich M, Zhang Q, Eisenstat DD, Erdélyi F, Baranyi M, Katarova ZD, Szabó G |title= GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: correlation with Dlx2 and Dlx5 |journal= Dev. Dyn. |volume= 236 |issue= 12 |pages= 3532–44 |date= December 2007 |pmid= 17969168 |doi= 10.1002/dvdy.21361|s2cid= 24188696 |doi-access= free }}</ref>