Sodium glucose transporters (SGLTs) belong to the mammalian solute carrier family SLC5. This family includes 12 different members in human that mediate the transport of sugars, vitamins, amino acids, or smaller organic ions such as choline. The SLC5 family belongs to the sodium symporter family (SSS), which encompasses transporters from all kingdoms of life. It furthermore shares similarity to the structural fold of the APC (amino acid-polyamine-organocation) transporter family. Three decades after the first molecular identification of the intestinal Na⁺-glucose cotransporter SGLT1 by expression cloning, many new discoveries have evolved, from mechanistic analysis to molecular genetics, structural biology, drug discovery, and clinical applications. All of these advances have greatly influenced physiology and medicine. While SGLT1 is essential for fast absorption of glucose and galactose in the intestine, the expression of SGLT2 is largely confined to the early part of the kidney proximal tubules, where it reabsorbs the bulk part of filtered glucose. SGLT2 has been successfully exploited by the pharmaceutical industry to develop effective new drugs for the treatment of diabetic patients. These SGLT2 inhibitors, termed gliflozins, also exhibit favorable nephroprotective effects and likely also cardioprotective effects. In addition, given the recent finding that SGLT2 is also expressed in tumors of pancreas and prostate and in glioblastoma, this opens the door to potential new therapeutic strategies for cancer treatment by specifically targeting SGLT2. Likewise, further discoveries related to the functional association of other SGLTs of the SLC5 family to human pathologies will open the door to potential new therapeutic strategies. We furthermore hope that the herein summarized information about the physiological roles of SGLTs and the therapeutic benefits of the gliflozins will be useful for our readers to better understand the molecular basis of the beneficial effects of these inhibitors, also in the context of the tubuloglomerular feedback (TGF), and the renin-angiotensin system (RAS). The detailed mechanisms underlying the clinical benefits of SGLT2 inhibition by gliflozins still warrant further investigation that may serve as a basis for future drug development.

钠葡萄糖转运蛋白 (SGLT) 属于哺乳动物溶质载体家族 SLC5。该家族包括人体中 12 种不同的成员，它们介导糖、维生素、氨基酸或较小的有机离子（如胆碱）的运输。 SLC5 家族属于钠同向转运蛋白家族 (SSS)，该家族涵盖所有生命领域的转运蛋白。此外，它与 APC（氨基酸-多胺-有机阳离子）转运蛋白家族的结构折叠相似。首次通过表达克隆对肠道 Na ^{+ -}葡萄糖协同转运蛋白 SGLT1 进行分子鉴定三十年后，从机制分析到分子遗传学、结构生物学、药物发现和临床应用，许多新发现不断涌现。所有这些进步都极大地影响了生理学和医学。虽然 SGLT1 对于肠道中葡萄糖和半乳糖的快速吸收至关重要，但 SGLT2 的表达主要局限于肾近端小管的早期部分，在那里它重新吸收大部分滤过的葡萄糖。 SGLT2已被制药行业成功开发用于治疗糖尿病患者的有效新药。这些 SGLT2 抑制剂（称为格列净）也表现出良好的肾保护作用，也可能具有心脏保护作用。此外，鉴于最近发现 SGLT2 也在胰腺和前列腺肿瘤以及胶质母细胞瘤中表达，这为专门针对 SGLT2 的癌症治疗潜在新治疗策略打开了大门。同样，有关 SLC5 家族其他 SGLT 与人类病理学功能关联的进一步发现将为潜在的新治疗策略打开大门。 我们还希望本文总结的关于 SGLT 的生理作用和格列净的治疗益处的信息将有助于我们的读者更好地理解这些抑制剂有益作用的分子基础，也在肾小球反馈的背景下。 TGF）和肾素-血管紧张素系统（RAS）。格列净抑制 SGLT2 的临床益处的详细机制仍需要进一步研究，这可能作为未来药物开发的基础。