Gamma-aminobutyric acid in endocrine and metabolic regulation: implications for diabetes mellitus

Abstract

Gamma-aminobutyric acid (GABA), traditionally recognized as the main inhibitory neurotransmitter in the central nervous system, has a wide range of extraneuronal effects, including regulatory roles in endocrine functions and metabolic processes, as demonstrated by increasingly new data. This review summarizes the molecular mechanisms of GABA biosynthesis and metabolism, the classification and tissue distribution of its receptors, and the functional properties of the GABAergic system in the pancreas, adrenal glands, gonads, thyroid gland, gastrointestinal tract, and vascular system. Particular attention is placed on the involvement of GABA in the pathogenesis of type 1 and type 2 diabetes mellitus, emphasizing its immunomodulatory, regenerative, and metabolic effects. These include effects on insulin secretion, insulin resistance, gluconeogenesis, and lipogenesis. The cytoprotective effects of GABA on pancreatic β-cells, its participation in PI3K/Akt signaling pathways, and the modulation of transcription factor expression are discussed. Moreover, the role of the gut microbiota as an exogenous source of GABA, and its potential involvement in the gut-brain axis, is under consideration. Available evidence suggests that GABA has significant therapeutic potential in diabetes mellitus and metabolic disorders, warranting further investigation.