Ukr.Biochem.J. 2026; Volume 98, Issue 1, Jan-Feb, pp. 20-29

doi: https://doi.org/10.15407/ubj98.01.020

GABA-ergic system in the experimental diabetes

11.02.2026   Uncategorized

H. L. Hayrapetyan, N. Kh. Khachatryan, R. R. Balagyozyan,
V. R. Balagyozyan, S. S. Mardanyan*, A. A. Antonyan

Department of Metabolism of Adenylic Compounds,
H. Buniatian Institute of Biochemistry of Armenian NAS, Yerevan, Armenia;
*e-mail: biochem@biochem.sci.am

Received: 09 September 2025; Revised: 22 October 2025;
Accepted: 30 January 2026; Available on-line: 23 February 2026

γ-Aminobutyric acid (GABA) is a non-proteinogenic amino acid, neurotransmitter and concurrently trophic factor in the non-neuronal peripheral tissues. GABA is involved in the pathophysiology of endocrine disorders, in particular, diabetes mellitus (DM). This review summarizes the effects of GABA-ergic system components on the development of experimental diabetes induced in laboratory animals. The beneficial effect of GABA-associated amino acids mixtures in the DM treatment is discussed.

Keywords: , , , ,

References:

  1. Wilcox G. Insulin and insulin resistance. Clin Biochem Rev. 2005;26(2):19-39. PubMed, PubMedCentral
  2. Yanagisawa Y. How dietary amino acids and high protein diets influence insulin secretion. Physiol Rep. 2023;11(2):e15577. PubMed, PubMedCentral, CrossRef
  3. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2009;32(Suppl 1):S62-S67. PubMed, PubMedCentral, CrossRef
  4. Balagyozyan RR, Karapetyan LG, Sharoyan SG, Antonyan AA, Agajanova EM, Mardanyan SS. Characteristics of some enzymes in blood plasma of diabetic humans. Proc YSU B Chem Biol Sci. 2023; 57(3): 269-281. CrossRef
  5. Banday MZ, Sameer AS, Nissar S. Pathophysiology of diabetes: An overview. Avicenna J Med. 2020;10(4):174-188. PubMed, PubMedCentral, CrossRef
  6.  van Harten B, de Leeuw FE, Weinstein HC, Scheltens P, Biessels GJ. Brain imaging in patients with diabetes: a systematic review. Diabetes Care. 2006;29(11):2539-2548. PubMed, CrossRef
  7. Wootton-Gorges SL, Glaser NS. Imaging of the brain in children with type I diabetes mellitus. Pediatr Radiol. 2007;37(9):863-869. PubMed, CrossRef
  8. Jongen C, Biessels GJ. Structural brain imaging in diabetes: a methodological perspective. Eur J Pharmacol. 2008;585(1):208-218. PubMed, CrossRef
  9. Zsombok A, Smith BN. Plasticity of central autonomic neural circuits in diabetes. Biochim Biophys Acta. 2009;1792(5):423-431. PubMed, PubMedCentral, CrossRef
  10. 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. GABA promotes human β-cell proliferation and modulates glucose homeostasis. Diabetes. 2014;63(12):4197-4205. PubMed, CrossRef
  11. Gladkevich A, Korf J, Hakobyan VP, Melkonyan KV. The peripheral GABAergic system as a target in endocrine disorders. Auton Neurosci. 2006;124(1-2):1-8. PubMed, CrossRef
  12. Kash SF, Condie BG, Baekkeskov S. Glutamate decarboxylase and GABA in pancreatic islets: lessons from knock-out mice. Horm Metab Res. 1999;31(5):340-344. PubMed, CrossRef
  13. Tian J, Dang H, Middleton B, Kaufman DL. Clinically applicable GABA receptor positive allosteric modulators promote ß-cell replication. Sci Rep. 2017;7(1):374.
    PubMed, PubMedCentral, CrossRef
  14. Raster P, Späth A, Bultakova S, Gorostiza P, König B, Bregestovski P. New GABA amides activating GABAA-receptors. Beilstein J Org Chem. 2013;9:406-410. PubMed, PubMedCentral, CrossRef
  15. Kamalyan RG, Vardanyan AG. GABA and GABA amide metabolism in the brain. Neurochem J. 2012;6(2):100-103. CrossRef
  16. Kamalyan RG. The possible new way of GABA formation in brain. Electronic J Nat Sci NAS RA Armenia. 2007;9(2):14-18.
  17. 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. GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes. Proc Natl Acad Sci USA. 2011;108(28):11692-11697. PubMed, PubMedCentral, CrossRef
  18. Tian J, Dang H, Chen Z, Guan A, Jin Y, Atkinson MA, Kaufman DL. γ-Aminobutyric acid regulates both the survival and replication of human β-cells. Diabetes. 2013;62(11):3760-3765. PubMed, PubMedCentral, CrossRef
  19. Korol SV, Jin Z, Jin Y, Bhandage AK, Tengholm A, Gandasi NR, Barg S, Espes D, Carlsson PO, Laver D, Birnir B. Functional Characterization of Native, High-Affinity GABAA Receptors in Human Pancreatic β Cells. EBioMedicine. 2018;30:273-282. PubMed, PubMedCentral, CrossRef
  20. Mendu SK, Bhandage A, Jin Z, Birnir B. Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes. PLoS One. 2012;7(8):e42959. PubMed, PubMedCentral, CrossRef
  21. 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. Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis. Cell. 2017;168(1-2):73-85.e11. PubMed, CrossRef
  22. Franklin IK, Wollheim CB. GABA in the endocrine pancreas: its putative role as an islet cell paracrine-signalling molecule. J Gen Physiol. 2004;123(3):185-190. PubMed, PubMedCentral, CrossRef
  23. Khachatryan N. Pathways of amide metabolism in the pancreas. Biol J Arm. 2019;71(2):62-65.
  24. Kamalyan RG, Vardanyan AG, Khachatryan NKh, Grigoryan AG. Some features of dicarboxylic amino acid metabolism in the rat brain. Rep NAS Armenia. 2013;113(1):59-65.
  25. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res. 2001;50(6):537-546. PubMed, CrossRef
  26. Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 2008;51(2):216-226. PubMed, CrossRef
  27. Lenzen S. Alloxan and streptozotocin diabetes. Adv Res Institutes of Diab Anim. 2010;6(4):113-122.
  28. Khachatryan NKh. Comparative effect of diabetogens on the content of neuroactive amino acids in the brain and pancreas of rats. Med Sci Armenia. 2020;60(2):38-44.
  29. tarr MS, Tanner T. Effects of amino-oxyacetic acid, ethanolamine-O-sulphate and GABA on the contents of GABA and various amines in brain slices. J Neurochem. 1975;25(5):573-577. PubMed, CrossRef
  30. Qume M, Fowler LJ. Effect of chronic treatment with the GABA transaminase inhibitors gamma-vinyl GABA and ethanolamine O-sulphate on the in vitro GABA release from rat hippocampus. Br J Pharmacol. 1997;122(3):539-545. PubMed, PubMedCentral, CrossRef
  31. Geisler CE, Ghimire S, Bruggink SM, Miller KE, Weninger SN, Kronenfeld JM, Yoshino J, Klein S, Duca FA, Renquist BJ. A critical role of hepatic GABA in the metabolic dysfunction and hyperphagia of obesity. Cell Rep. 2021;35(13):109301. PubMed, PubMedCentral, CrossRef
  32. Khachatryan NKh, Vardanyan AG, Taroyan SG, Khachatryan RS, Kamalyan RG. Effect of ethanolamine-O-sulfate on the content of neuroactive amino acids in the organs of rats under normal conditions and in experimental alloxan diabetes. Biol J Arm. 2017;69(1):68-72.
  33. Araya S, Kuster E, Gluch D, Mariotta L, Lutz C, Reding TV, Graf R, Verrey F, Camargo SMR. Exocrine pancreas glutamate secretion help to sustain enterocyte nutritional needs under protein restriction. Am J Physiol Gastrointest Liver Physiol. 2018;314(4):G517-G536. PubMed, CrossRef
  34. Taroyan SK, Khachatryan RS, Khachatryan NKh, Vardanyan AG, Kamalyan RG. On the exchange of neuroactive amino acids in the mitochondria of the brain and pancreas in normal conditions and in experimental diabetes. International Youth Conference Dedicated to the 110-th Anniversary of Academician H. Buniatian, Collection of Articles, Yerevan, 2017; 57-65.
  35. Kamalyan RG, Khachatryan RS, Khachatryan NKh. An attempt to prevent experimental streptozotocin diabetes. Biol J Armenia. 2019;71(1):73-78.
  36. Pochini L, Scalise M, Galluccio M, Indiveri C. Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health. Front Chem. 2014;2:61. PubMed, PubMedCentral, CrossRef
  37. Jafari-Vayghan H, Varshosaz P, Hajizadeh-Sharafabad F, Razmi HR, Amirpour M, Tavakoli-Rouzbehani OM, Alizadeh M, Maleki V. A comprehensive insight into the effect of glutamine supplementation on metabolic variables in diabetes mellitus: a systematic review. Nutr Metab (Lond). 2020;17:80. PubMed, PubMedCentral, CrossRef
  38. Mauras N, Xing D, Fox LA, Englert K, Darmaun D. Effects of glutamine on glycemic control during and after exercise in adolescents with type 1 diabetes: a pilot study. Diabetes Care. 2010;33(9):1951-1953. PubMed, PubMedCentral, CrossRef
  39. Kamalyan RG, Khachatryan NKh, Vardanyan AG, Taroyan SQ, Eritsyan LN. The influence of glutamine and ethanolamine-O-sulfate on neuroactive amino acids content in the rat organs in norm and with experimental streptozotocine diabetes. Biolog J Arm. 2015;67(3):61-60.
  40. Capasso R, Izzo AA. Gastrointestinal regulation of food intake: general aspects and focus on anandamide and oleoylethanolamide. J Neuroendocrinol. 2008;20(Suppl 1):39-46. PubMed, CrossRef
  41. Kamalyan RG, Harutyunyan AA, Khachatryan NKh, Vardanyan AG, Taroyan SG. Effect of GABA-generating factors on the level of neuroactive amino acids in streptozotocin-induced diabetic rats. Med Sci Armenia. 2015;55(4):32-42.
  42. Khachatryan RS, Khachatryan NKh, Kamalyan RG. Antidiabetic effect of a complex of neuroactive amino acids on the alloxan diabetes model. Biol J Arm. 2019;71(4):66-69.
  43. Paronyan ZKh, Khachatryan HS, Stepanyan HA, Grigoryan LS, Araqelyan LN. Alteration of glucose level and some hemostasis parameters under the action of the new amino acid complex in rats with experimental alloxan diabets. Med Sci Armenia. 2021;61(3):64-72.
  44. Paronyan ZKh, Arakelyan LN, Arakelyan LN Khachatryan RS, Galstyan AZ, Stepanyan AA. Effect of antidiabetic amino acid complex on some parameters of plasma hemostasis. Med Sci Armenia. 2023;63(3):64-71. CrossRef
  45. Paronyan Z, Sahakyan I, Stepanyan H, Tumasyan N, Araqelyan L, Kocharyan N, Suqiasyan A, Seferyan T, Grigoryan L, Abrahamyan S. Effects of the Amino Acid Complex on Biochemical and Morphological Parameters of Hemostasis at Chronic Cadmium Intoxication. Iran J Blood Cancer. 2024;16(4):39-46. CrossRef
  46. Vangipurapu J, Stancáková A, Smith U, Kuusisto J, Laakso M. Nine Amino Acids Are Associated With Decreased Insulin Secretion and Elevated Glucose Levels in a 7.4-Year Follow-up Study of 5,181 Finnish Men. Diabetes. 2019;68(6):1353-1358. PubMed, CrossRef
  47. Khachatryan NKh. On the metabolism of asparagine in the preparations of rat brain tissue. In “Innovative development and demand for science in modern Kazakhstan”. IV International scientific conference, Collection of articles, Almaty. 2012; 99-102.
  48. Zhu Y, Li T, Ramos da Silva S, Lee JJ, Lu C, Eoh H, Jung JU, Gao SJ. A Critical Role of Glutamine and Asparagine γ-Nitrogen in Nucleotide Biosynthesis in Cancer Cells Hijacked by an Oncogenic Virus. mBio. 2017;8(4):e01179-17. PubMed, PubMedCentral, CrossRef
  49. Luo HH, Feng XF, Yang XL, Hou RQ, Fang ZZ. Interactive effects of asparagine and aspartate homeostasis with sex and age for the risk of type 2 diabetes risk. Biol Sex Differ. 2020;11(1):58. PubMed, PubMedCentral, CrossRef
  50. Khachatryan N, Balagyozyan R, Balagyozyan V, Hekimyan G, Grigoryan G, Mardanyan S, Antonyan A. Antidiabetic effect of a GABA-supporting mixture in a streptozotocin-induced diabetes model in rats. Rom J Diabetes Nutr Metab Dis. 2024;31(4):371-378. CrossRef
Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.