Antoni Ferenc A
Centre of Discovery Brain Sciences, Deanery of Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK.
Life (Basel). 2022 Feb 21;12(2):322. doi: 10.3390/life12020322.
Obesity and diabetes mellitus have become the surprising menaces of relative economic well-being worldwide. Gamma amino butyric acid (GABA) has a prominent role in the control of blood glucose, energy homeostasis as well as food intake at several levels of regulation. The effects of GABA in the body are exerted through ionotropic GABA and metabotropic GABA receptors. This treatise will focus on the pharmacologic targeting of GABA receptors to reap beneficial therapeutic effects in diabetes mellitus and obesity. A new crop of drugs selectively targeting GABA receptors has been under investigation for efficacy in stroke recovery and cognitive deficits associated with schizophrenia. Although these trials have produced mixed outcomes the compounds are safe to use in humans. Preclinical evidence is summarized here to support the rationale of testing some of these compounds in diabetic patients receiving insulin in order to achieve better control of blood glucose levels and to combat the decline of cognitive performance. Potential therapeutic benefits could be achieved (i) By resetting the hypoglycemic counter-regulatory response; (ii) Through trophic actions on pancreatic islets, (iii) By the mobilization of antioxidant defence mechanisms in the brain. Furthermore, preclinical proof-of-concept work, as well as clinical trials that apply the novel GABA compounds in eating disorders, e.g., olanzapine-induced weight-gain, also appear warranted.
肥胖和糖尿病已成为全球相对经济福祉的惊人威胁。γ-氨基丁酸（GABA）在血糖控制、能量稳态以及多个调节层面的食物摄入控制中发挥着重要作用。GABA在体内的作用是通过离子型GABA受体和代谢型GABA受体来实现的。本论文将聚焦于GABA受体的药物靶向作用，以在糖尿病和肥胖症中获得有益的治疗效果。一批选择性靶向GABA受体的新型药物正在研究其对中风恢复以及与精神分裂症相关的认知缺陷的疗效。尽管这些试验结果不一，但这些化合物在人体中使用是安全的。本文总结了临床前证据，以支持在接受胰岛素治疗的糖尿病患者中测试其中一些化合物的合理性，以便更好地控制血糖水平并对抗认知能力下降。潜在的治疗益处可以通过以下方式实现：（i）重置低血糖反调节反应；（ii）通过对胰岛的营养作用；（iii）通过调动大脑中的抗氧化防御机制。此外，临床前概念验证工作以及将新型GABA化合物应用于饮食失调（如奥氮平引起的体重增加）的临床试验似乎也很有必要。
