2.A.21.3.16
Sodium/glucose cotransporter 2 (Na⁺/glucose cotransporter 2; SGLT2) of 672 aas and 14 TMSs. It is a low affinity sodium-glucose cotransporter). It shows increased expression in human diabetic nephropathy. Inhibition causes decreased renal lipid accumulation, inflamation and disease symptoms (Wang et al. 2017). 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. 2021). 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. 2022 determined the cryoEM 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. 2022 ). 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).  The effectiveness of sodium-glucose co-transporter 2 inhibitors on cardiorenal outcomes has been described (Niu et al. 2022 ). 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).  The effectiveness of sodium-glucose co-transporter 2 inhibitors on cardiorenal outcomes has been described (Ali et al. 2024).