Theory Department, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.
Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
Molecules. 2023 Jul 8;28(14):5295. doi: 10.3390/molecules28145295.
Sodium glucose cotransporters (SGLTs) are cotransporters located in the cell membrane of various epithelia that uptake glucose or galactose and sodium into the cell. Its founding member, SGLT1, represents a major pharmaceutically relevant target protein for development of new antidiabetic drugs, in addition to being the target protein of the oral rehydration therapy. Previous studies focused primarily on the transport of substrates and ions, while our study focuses on the effect of water transport. SGLT1 is implicated in the absorption of water, yet the exact mechanism of how the water absorption occurs or how inhibitors of SGLT1, such as phlorizin, are able to inhibit it is still unclear. Here we present a comprehensive study based on molecular dynamics simulations with the aim of determining the influence of the energetic and dynamic properties of SGLT1, which are influenced by selected sugar uptake inhibitors on water permeation.
钠-葡萄糖共转运蛋白（SGLTs）是位于各种上皮细胞膜上的共转运蛋白，可将葡萄糖或半乳糖和钠离子共转运到细胞内。其主要成员 SGLT1 是开发新型抗糖尿病药物的重要药物靶点，也是口服补液治疗的靶点蛋白。以前的研究主要集中在底物和离子的转运上，而我们的研究则侧重于水转运的影响。SGLT1 参与水的吸收，但水吸收的确切机制以及 SGLT1 的抑制剂（如根皮苷）如何能够抑制它尚不清楚。在这里，我们基于分子动力学模拟进行了一项全面的研究，旨在确定 SGLT1 的能量和动态特性的影响，这些特性受选定的糖摄取抑制剂对水渗透的影响。
