【GABA与降血糖药物的协同作用】。

Q4 Medicine
I N Tyurenkov, T I Faibisovich, D A Bakulin
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引用次数: 0

摘要

糖尿病(DM)是过早死亡和致残的主要原因。尽管有大量药物,但旨在使血糖水平正常化和预防并发症的治疗效果并不能完全让医生和患者满意。因此,寻找预防和治疗糖尿病及其并发症的新方法仍在继续。大量资源被用于开发新药,但最近使用具有新发现的多效性的“老”广泛可用药物的可能性得到了证实。其中可能包括γ-氨基丁酸(GABA)的制剂和直接或间接激活GABA能传递的药物,这些药物具有显著的胰腺保护作用,在过去10-15年中,国外文献对此进行了广泛讨论。然而,国内文献中很少有这样的出版物。已经证实,1型和2型糖尿病患者β细胞中GABA的含量降低,这与疾病的严重程度相关。GABA受体的遗传抑制导致β细胞质量和葡萄糖刺激的胰岛素分泌显著减少,这证实了GABA在确保葡萄糖稳态方面的重要性,以及通过额外给药补充糖尿病GABA缺乏的可取性。已经证实,在患有糖尿病的动物中,GABA抑制细胞凋亡并刺激β细胞的再生,增加β细胞的质量和胰岛素的产生。已经获得的实验数据表明,当GABA与胰高血糖素样肽-1(GLP-1)受体激动剂、DPP-4抑制剂和钠-葡萄糖协同转运蛋白2(SGLT-2)抑制剂联合使用时,由于氧化和亚硝化应激、炎症、Klotho蛋白水平增加、,Nrf-2活性和抗氧化防御酶、抑制NF-kB活性和促炎细胞因子的表达。因此,所有这些都会导致β细胞凋亡和死亡的减少,β细胞质量和胰岛素产量的增加,同时胰高血糖素水平和胰岛素抵抗的降低。该综述证实了将GABA和具有正GABA作用的药物与新一代抗糖尿病药物(GLP-1受体激动剂、DPP-4抑制剂和SGLT-2抑制剂)联合使用以提高其抗糖尿病潜力的可行性。搜索是在Pubmed、eLibrary和Medline数据库中进行的。关键词:糖尿病,γ-氨基丁酸,胰高血糖素样肽-1,GLP-1受体激动剂,葡萄糖依赖性促胰岛素肽,二肽基肽酶抑制剂,钠-葡萄糖协同转运蛋白2抑制剂。搜索是在2000年至2022年进行的,但由于期刊对最大工作量和来源数量的要求,综述显示了主要在过去3年发表的研究结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Synergistic effects of GABA and hypoglycemic drugs].

Diabetes mellitus (DM) is the leading cause of premature death and disability. Despite a significant number of drugs, the effectiveness of therapy aimed at normalizing the level of glycemia and preventing complications does not fully satisfy doctors and patients. Therefore, the search for new approaches for the prevention and treatment of DM 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 substantiated. These may include preparations of gammaaminobutyric acid (GABA) and agents that directly or indirectly activate GABAergic transmission, which have a pronounced pancreatic protective effect, which has been widely discussed in foreign literature over the past 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 is reduced and this correlates with the severity of the disease. Genetic suppression of GABA receptors causes a significant decrease in the mass of β-cells and glucose-stimulated insulin secretion, which confirms the importance of GABA in ensuring glucose homeostasis and the advisability of replenishing the GABA deficiency in DM with its additional administration. It has been established that in animals with DM, GABA suppresses apoptosis and stimulates the regeneration of β-cells, increases β-cell mass and insulin production.Experimental data have been obtained indicating a synergistic effect of GABA when combined with glucagon-like peptide-1 (GLP-1) receptor agonists, DPP-4 inhibitors and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, when a more pronounced pancreoprotective effect is observed, due to decrease in oxidative and nitrosative stress, inflammation, increase in the level of Klotho protein, Nrf-2 activity and antioxidant defense enzymes, suppression of NF-kB activity and 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 and insulin resistance.The review substantiates the feasibility of using GABA and drugs with a positive GABAeric effect in combination with new generation antidiabetic agents: GLP-1 receptor agonists, DPP-4 inhibitors and SGLT-2 inhibitors in order to increase their antidiabetic potential.The search was carried out in the databases Pubmed, eLibrary, Medline. Keywords: diabetes mellitus, gamma-aminobutyric acid, glucagon-like peptide-1, GLP-1 receptor agonists, glucose-dependent insulinotropic peptide, dipeptidyl peptidase inhibitors, sodium-glucose cotransporter 2 inhibitors. The search was carried out from 2000 to 2022, but the review presents the results studies published mainly in the last 3 years, due to the requirements of the journal for the maximum amount of work and the number of sources.

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来源期刊
Problemy endokrinologii
Problemy endokrinologii Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
1.40
自引率
0.00%
发文量
59
期刊介绍: Since 1955 the “Problems of Endocrinology” (or “Problemy Endocrinologii”) Journal publishes timely articles, balancing both clinical and experimental research, case reports, reviews and lectures on pressing problems of endocrinology. The Journal is aimed to the most topical issues of endocrinology: to chemical structure, biosynthesis and metabolism of hormones, the mechanism of their action at cellular and molecular level; pathogenesis and to clinic of the endocrine diseases, new methods of their diagnostics and treatment. The Journal: features original national and foreign research articles, reflecting world endocrinology development; issues thematic editions on specific areas; publishes chronicle of major international congress sessions and workshops on endocrinology, as well as state-of-the-art guidelines; is intended for scientists, endocrinologists diabetologists and specialists of allied trade, general practitioners, family physicians and pediatrics.
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