2.A.1.7.26
Na⁺:glucose co-transporter of 672 aas and about 14 TMSs, SGLT2. It has a Na⁺ to glucose coupling ratio of 1:1 (Brown et al. 2019). Efficient substrate transport in the mammalian kidney is provided by the concerted action of a low affinity high capacity and a high affinity low capacity Na⁺/glucose cotransporter arranged in series along kidney proximal tubules. Inhibitors are antidiabetic agents (Li 2019; Singh and Singh 2020). They are also useful as theraputic agents of non-alcoholic fatty liver disease and chronic kidney disease (Kanbay et al. 2020). Marein, an active component of the Coreopsis tinctoria Nutt plant, ameliorates diabetic nephropathy by inhibiting renal sodium glucose transporter 2 and activating the AMPK signaling pathway (Guo et al. 2020). NHE-3 (TC# 2.A.53.2.18) was markedly downregulated, while the Na⁺-HCO₃^--cotransporter (NBC-1; TC# 2.A.31.2.12) and SGLT2 were upregulated after kidney transplantation (Velic et al. 2004). Pharmacological inhibition of hSGLT2 by oral small-molecule inhibitors, such as empagliflozin, leads to enhanced excretion of glucose and is widely used in the clinic to manage blood glucose levels for the treatment of type 2 diabetes. Niu et al. 2021 determined the cryogenic electron microscopic structure of the hSGLT2-MAP17 complex in the empagliflozin-bound state to a resolution of 2.95 Å. MAP17 interacts with transmembrane helix 13 of hSGLT2. Empagliflozin occupies both the sugar-substrate-binding site and the external vestibule to lock hSGLT2 in an outward-open conformation, thus inhibiting the transport cycle (Niu et al. 2021). There is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker, linagliptin, are used (Xiong et al. 2022). Canagliflozin, dapagliflozin and ipragliflozin significantly inhibit the growth of different cancer cell lines in the micromolar range; SGLT2 inhibitors have antiproliferation, anti-tumorigenesis, and anti-migration effects and may induce apoptosis in cancer cells. Treatment with SGLT2 inhibitors also results in the downregulation of selected genes (Bardaweel and Issa 2022). SGLT2 inhibitor treatment results in symptomatic and functional well-being, especially in relieving pain (Calderon-Rivera et al. 2022). Effects of SGLT2 inhibitors affect the heart and kidney to promote autophagic flux, nutrient deprivation signaling and transmembrane sodium transport (Zannad et al. 2022). Empagliflozin (EMPA), mainly acting on SGLT2, prevented DNA methylation changes induced by high glucose and provided evidence of a new mechanism by which SGLT2i can exert cardio-beneficial effects (Scisciola et al. 2023). A diversifiable synthetic platform for the discovery of new carbasugar SGLT2 inhibitors using azide-alkyne click chemistry has been described (Kitamura et al. 2023). SGLT2 is inhibited by empagliflozin (Raven et al. 2023). SGLT2 inhibitors not only suppress hyperglycemia but also reduce renal, heart, and cardiovascular diseases (Unno et al. 2023). In fact, SGLT2 may also be related to other functions, such as bone metabolism, longevity, and cognitive functions based on mouse models (Unno et al. 2023). Complex effects of different SGLT2 inhibitors on alphaKlotho gene expression (see TC family 8.A.49) and protein secretion in renal MDCK and HK-2 cells have been observed (Wolf et al. 2023). Ferulic acid-grafted chitosan (FA-g-CS) stimulates the transmembrane transport of anthocyanins by SGLT1 and GLUT2 (Ma et al. 2022). SGLT2 Inhibitors are potential anticancer agents (Basak et al. 2023). Analyses of the effects of SGLT2 inhibitors on renal tubular sodium, water and chloride homeostasis as well as their roles in influencing heart failure outcomes has appeared (Packer et al. 2023).  The SGLT2 inhibitor, empagliflozin, alleviates cardiac remodeling and contractile anomalies in a FUNDC1-dependent manner in experimental Parkinson's disease (Yu et al. 2023). Type 2 diabetes guidance proposes offering SGLT2-inhibitor therapy to people with established atherosclerotic cardiovascular disease (ASCVD) or heart failure, but this suggestion has been questioned (Young et al. 2023). SGLT2 inhibition in a non-diabetic rat model of salt-sensitive hypertension blunts the development of salt-induced hypertension independent of sex (Kravtsova et al. 2023).