Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 St. Petersburg, Russia.
Int J Mol Sci. 2023 Feb 7;24(4):3278. doi: 10.3390/ijms24043278.
A decrease in the activity of the insulin signaling system of the brain, due to both central insulin resistance and insulin deficiency, leads to neurodegeneration and impaired regulation of appetite, metabolism, endocrine functions. This is due to the neuroprotective properties of brain insulin and its leading role in maintaining glucose homeostasis in the brain, as well as in the regulation of the brain signaling network responsible for the functioning of the nervous, endocrine, and other systems. One of the approaches to restore the activity of the insulin system of the brain is the use of intranasally administered insulin (INI). Currently, INI is being considered as a promising drug to treat Alzheimer's disease and mild cognitive impairment. The clinical application of INI is being developed for the treatment of other neurodegenerative diseases and improve cognitive abilities in stress, overwork, and depression. At the same time, much attention has recently been paid to the prospects of using INI for the treatment of cerebral ischemia, traumatic brain injuries, and postoperative delirium (after anesthesia), as well as diabetes mellitus and its complications, including dysfunctions in the gonadal and thyroid axes. This review is devoted to the prospects and current trends in the use of INI for the treatment of these diseases, which, although differing in etiology and pathogenesis, are characterized by impaired insulin signaling in the brain.
大脑胰岛素信号系统的活性下降,这是由于中枢性胰岛素抵抗和胰岛素缺乏所致,导致神经退行性变和食欲、代谢、内分泌功能受损。这是由于脑胰岛素具有神经保护特性及其在维持脑内葡萄糖稳态以及调节负责神经、内分泌和其他系统功能的大脑信号网络方面的主导作用。恢复大脑胰岛素系统活性的方法之一是使用经鼻给予的胰岛素(INI)。目前,INI 被认为是治疗阿尔茨海默病和轻度认知障碍的有前途的药物。正在开发 INI 的临床应用,以治疗其他神经退行性疾病并改善应激、过度劳累和抑郁时的认知能力。与此同时,最近人们对使用 INI 治疗脑缺血、创伤性脑损伤和术后谵妄(麻醉后)以及糖尿病及其并发症(包括性腺和甲状腺轴功能障碍)的前景给予了极大关注。这篇综述专门讨论了 INI 治疗这些疾病的前景和当前趋势,尽管这些疾病的病因和发病机制不同,但它们的特点是大脑胰岛素信号受损。