钠-葡萄糖共转运蛋白1和2的研究新进展

New perspectives on research of sodium-glucose cotransporters 1 and 2

钠-葡萄糖共转运蛋白(sodium-glucose cotransporters,SGLTs)是一类在小肠黏膜和肾近曲小管中发现的葡萄糖转运蛋白家族,其功能是介导肾脏和肠道中葡萄糖的跨膜转运.近几年研究表明,SGLT2是控制葡萄糖在肾脏重吸收的重要转运子,其抑制剂不仅可以增加尿糖的排泄从而控制糖尿病患者血糖,而且可以降低血压进而起到保护心血管的作用.而SGLT1在SGLT2抑制后,可以代偿肾脏对葡萄糖的重吸收而削弱SGLT2抑制剂的降糖疗效,同时SGLT1也是肠道吸收葡萄糖的主要转运子,因此SGLT2抑制剂对糖尿病也有治疗前景,另外,SGLT1的表达受到胃肠激素如胰高血糖素样肽-1的调控,并与味觉受体相互作用,从而对人的摄食行为和食欲产生影响,参与肥胖的发病机制.本文主要综述了SGLTs的生理功能,及其与味觉受体、肠道激素相互作用,并对其作为糖尿病治疗的新靶点进行展望.

Sodium-glucose cotransporters（SGLTs） are a family of glucose transporters located in the mucosa of the small intestine and the proximal tubule of the nephron.They are important mediators of glucose uptake across cell membranes.According to recent basic studies and clinical trials,SGLT2 controls renal glucose reabsorption and its inhibitors not only act as antihyperglycemia agents via increment of urinary glucose excretion but also decrease blood pressure to exert a cardioprotective effect.When SGLT2 is inhibited,SGLT1 compensates for the function of SGLT2 in renal glucose reabsorption,weakening the hypoglycemic action of SGLT2 inhibitors.In the small intestine,SGLT1 also mediates almost the whole sodium-dependent glucose uptake.As a result,SGLT1 inhibitors have therapeutic potential for diabetes.In addition,the expression of SGLT1 is associated with gastrointestinal hormones such as glucagon-like peptide 1（GLP-1） and taste receptors.Therefore,it can have an impact on human feeding behaviors and appetite and be involved in the pathogenesis of obesity.This review focuses on the physiological functions of SGLT1 and SGLT2,their interaction with taste receptors and intestinal hormone,and their prospects as new therapeutic targets for diabetes management.