SGLT1:心血管疾病的潜在药物靶点。

SGLT1: A Potential Drug Target for Cardiovascular Disease.

机构信息

Department of Endocrinology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

出版信息

Drug Des Devel Ther. 2023 Jul 6;17:2011-2023. doi: 10.2147/DDDT.S418321. eCollection 2023.

Abstract

SGLT1 and SGLT2 are the two main members of the sodium-glucose cotransporters (SGLTs), which are mainly responsible for glucose reabsorption in the body. In recent years, many large clinical trials have shown that SGLT2 inhibitors have cardiovascular protection for diabetic and non-diabetic patients independent of lowering blood glucose. However, SGLT2 was barely detected in the hearts of humans and animals, while SGLT1 was highly expressed in myocardium. As SGLT2 inhibitors also have a moderate inhibitory effect on SGLT1, the cardiovascular protection of SGLT2 inhibitors may be due to SGLT1 inhibition. SGLT1 expression is associated with pathological processes such as cardiac oxidative stress, inflammation, fibrosis, and cell apoptosis, as well as mitochondrial dysfunction. The purpose of this review is to summarize the protective effects of SGLT1 inhibition on hearts in various cell types, including cardiomyocytes, endothelial cells, and fibroblasts in preclinical studies, and to highlight the underlying molecular mechanisms of protection against cardiovascular diseases. Selective SGLT1 inhibitors could be considered a class of drugs for cardiac-specific therapy in the future.

摘要

SGLT1 和 SGLT2 是钠-葡萄糖协同转运蛋白(SGLTs)的两个主要成员,主要负责体内葡萄糖的重吸收。近年来,许多大型临床试验表明,SGLT2 抑制剂对糖尿病和非糖尿病患者具有独立于降血糖之外的心血管保护作用。然而,SGLT2 在人和动物的心脏中几乎检测不到,而 SGLT1 在心肌中高度表达。由于 SGLT2 抑制剂对 SGLT1 也有适度的抑制作用,因此 SGLT2 抑制剂的心血管保护作用可能归因于 SGLT1 抑制。SGLT1 的表达与心脏的氧化应激、炎症、纤维化和细胞凋亡等病理过程以及线粒体功能障碍有关。本综述的目的是总结 SGLT1 抑制在各种细胞类型(包括心肌细胞、内皮细胞和成纤维细胞)的心脏中的保护作用的临床前研究,并强调其对心血管疾病的保护作用的潜在分子机制。选择性 SGLT1 抑制剂将来可能被认为是一种心脏特异性治疗的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7536/10332373/cfc0161c7b67/DDDT-17-2011-g0001.jpg

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