INTERACTIONS OF GABA AND HYPOGLYCEMIC DRUGS

Annotatsiya

Diabetes mellitus (DM) is a leading cause of premature mortality and disability. Despite a significant number of drugs, the effectiveness of therapy aimed at normalizing glycemic levels and preventing complications does not fully satisfy doctors and patients. Therefore, the search for new approaches for the prevention and treatment of diabetes and its complications continues. Significant resources are used to develop new drugs, but recently the possibility of using “old” widely available drugs with newly discovered pleiotropic properties has been justified. These may include gamma-aminobutyric acid (GABA) preparations and agents that directly or indirectly activate GABAergic transmission, which have a pronounced pancreoprotective effect, which has been widely discussed in foreign literature in the last 10–15 years. However, there are few such publications in the domestic literature. It has been established that the content of GABA in β-cells in patients with type 1 and type 2 diabetes decreases, and this correlates with the severity of the disease. Genetic suppression of GABAA receptors causes a significant decrease in β-cell mass and glucose-stimulated insulin secretion, which confirms the importance of GABA in ensuring glucose homeostasis and the advisability of replenishing GABA deficiency in diabetes with its additional administration. It has been established that in animals with diabetes, GABA suppresses apoptosis and stimulates the regeneration of β-cells, increases β-cell mass and insulin production. Experimental data have been obtained indicating the synergistic effect of GABA when combined with glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase type 4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, when a more pronounced pancreoprotective effect is observed, due to a decrease in oxidative and nitrosative stress, inflammation, an increase in the level of Klotho protein, Nrf-2 activity and antioxidant defense enzymes, suppression of NF-kB activity and the expression of pro-inflammatory cytokines. As a result, all this leads to a decrease in apoptosis and death of β-cells, an increase in β-cell mass, insulin production and at the same time a decrease in glucagon levels,insulin resistance.