Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2.
Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2.
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DOI：
10.1007/s00125-018-4656-5
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发表时间：
2018-10
期刊：
影响因子：
8.2
通讯作者：
Wright EM
中科院分区：
文献类型：
--
作者：
Ghezzi C;Loo DDF;Wright EM
血浆中葡萄糖的浓度保持在较窄的范围内（4-10 mmol/l），主要是为了确保大脑的燃料供应。肾脏通过确保葡萄糖不会在尿液中丢失而在体内葡萄糖稳态中发挥作用。三种膜蛋白负责近端小管中肾小球滤液的葡萄糖重吸收：钠-葡萄糖协同转运蛋白SGLT 1和SGLT 2，位于顶膜; GLUT 2，位于基底外侧膜。在小鼠和人中“敲除”这些转运蛋白会导致过滤后的葡萄糖在尿液中排泄。在人类中，静脉注射植物葡萄糖苷根皮苷也会导致全部过滤葡萄糖负荷的排泄。这一结果以及根皮苷在动物模型中逆转糖尿病症状的发现，刺激了SGLT 2抑制剂格列净在2型糖尿病治疗中的开发和成功引入。在此，我们总结了我们对肾脏葡萄糖处理生理学的了解现状，并为SGLT 2抑制剂治疗2型糖尿病的开发提供了背景。本文的在线版本（10.1007/s 00125 -018-4656-5）包含一组可供下载的数字幻灯片，可供授权用户使用。
The concentration of glucose in plasma is held within narrow limits (4–10 mmol/l), primarily to ensure fuel supply to the brain. Kidneys play a role in glucose homeostasis in the body by ensuring that glucose is not lost in the urine. Three membrane proteins are responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule: sodium−glucose cotransporters SGLT1 and SGLT2, in the apical membrane, and GLUT2, a uniporter in the basolateral membrane. ‘Knockout’ of these transporters in mice and men results in the excretion of filtered glucose in the urine. In humans, intravenous injection of the plant glucoside phlorizin also results in excretion of the full filtered glucose load. This outcome and the finding that, in an animal model, phlorizin reversed the symptoms of diabetes, has stimulated the development and successful introduction of SGLT2 inhibitors, gliflozins, in the treatment of type 2 diabetes mellitus. Here we summarise the current state of our knowledge about the physiology of renal glucose handling and provide background to the development of SGLT2 inhibitors for type 2 diabetes treatment. The online version of this article (10.1007/s00125-018-4656-5) contains a slideset of the figures for download, which is available to authorised users.
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影响因子：
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