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阿尔茨海默病中的胰岛素和胰岛素抵抗。

Insulin and Insulin Resistance in Alzheimer's Disease.

机构信息

Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland.

出版信息

Int J Mol Sci. 2021 Sep 15;22(18):9987. doi: 10.3390/ijms22189987.

Abstract

Insulin plays a range of roles as an anabolic hormone in peripheral tissues. It regulates glucose metabolism, stimulates glucose transport into cells and suppresses hepatic glucose production. Insulin influences cell growth, differentiation and protein synthesis, and inhibits catabolic processes such as glycolysis, lipolysis and proteolysis. Insulin and insulin-like growth factor-1 receptors are expressed on all cell types in the central nervous system. Widespread distribution in the brain confirms that insulin signaling plays important and diverse roles in this organ. Insulin is known to regulate glucose metabolism, support cognition, enhance the outgrowth of neurons, modulate the release and uptake of catecholamine, and regulate the expression and localization of gamma-aminobutyric acid (GABA). Insulin is also able to freely cross the blood-brain barrier from the circulation. In addition, changes in insulin signaling, caused inter alia insulin resistance, may accelerate brain aging, and affect plasticity and possibly neurodegeneration. There are two significant insulin signal transduction pathways: the PBK/AKT pathway which is responsible for metabolic effects, and the MAPK pathway which influences cell growth, survival and gene expression. The aim of this study is to describe the role played by insulin in the CNS, in both healthy people and those with pathologies such as insulin resistance and Alzheimer's disease.

摘要

胰岛素在周围组织中作为一种合成代谢激素发挥多种作用。它调节葡萄糖代谢,刺激葡萄糖进入细胞的转运,并抑制肝葡萄糖生成。胰岛素影响细胞生长、分化和蛋白质合成,并抑制糖酵解、脂肪分解和蛋白水解等分解代谢过程。胰岛素和胰岛素样生长因子-1 受体存在于中枢神经系统的所有细胞类型上。在大脑中的广泛分布证实了胰岛素信号在该器官中发挥着重要而多样的作用。已知胰岛素可调节葡萄糖代谢、支持认知、促进神经元的生长、调节儿茶酚胺的释放和摄取,并调节γ-氨基丁酸(GABA)的表达和定位。胰岛素还能够从循环中自由穿过血脑屏障。此外,胰岛素信号的变化,如胰岛素抵抗,可能会加速大脑衰老,并影响可塑性,甚至神经退行性变。有两条重要的胰岛素信号转导途径:负责代谢效应的 PBK/AKT 途径,以及影响细胞生长、存活和基因表达的 MAPK 途径。本研究旨在描述胰岛素在中枢神经系统中的作用,包括在健康人群和胰岛素抵抗和阿尔茨海默病等病理人群中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d94/8472298/b54320df22f6/ijms-22-09987-g001.jpg

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