ABSTRACT
BACKGROUND: Diabetes mellitus (DM) is an endocrine disorder characterized by hyperglycemia, polyuria, polydipsia, and glucosuria. γ-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the central nervous system (CNS) of humans and other mammals. GABA acts on two different receptors, which are GABA-A and GABA-B. Pancreatic ß-cells synthesize GABA from glutamic acid by glutamic acid decarboxylase (GAD). AIM: The objective of this study was to explore the potential role of pancreatic GABA on glycemic indices in DM. METHODS: Evidence from experimental, preclinical, and clinical studies are evaluated for bidirectional relationships between pancreatic GABA and blood glucose disorders. A multiplicity of search strategies took on and assumed included electronic database searches of Medline and Pubmed using MeSH terms, keywords and title words during the search. RESULTS: The pancreatic GABA signaling system has a role in the regulation of pancreatic hormone secretions, inhibition of immune response, improve ß-cells survival, and change α cell into ß-cell. Moreover, a GABA agonist improves the antidiabetic effects of metformin. In addition, benzodiazepine receptor agonists improve pancreatic ß-cell functions through GABA dependent pathway or through modulation of pancreatic adenosine and glucagon-like peptide (GLP-1). CONCLUSIONS: Pancreatic GABA improves islet cell function, glucose homeostasis, and autoimmunity in DM. Orally administered GABA is safe for humans, and acts on peripheral GABA receptors and represents a new therapeutic modality for both T1DM and T2DM. Besides, GABA-A receptor agonist like benzodiazepines improves pancreatic ß-cell function and insulin sensitivity through activation of GABA-A receptors.
