摘要
随着对DM发病机制的深入研究,目前肾脏对血糖的调节作用逐渐受到关注。生理状态,肾脏对葡萄糖代谢的调节包括糖异生产生葡萄糖、对葡萄糖的摄取和利用及近端小管钠-葡萄糖协同转运蛋白(SGLT1、SGLT2)介导的葡萄糖重吸收,对维持血糖稳态起重要作用。然而,在T2DM患者肾脏存在广泛的糖调节异常:空腹及餐后状态肾脏糖异生及肾脏对葡萄糖的摄取均增加,肾脏葡萄糖重吸收增加。SGLT2是近端小管介导葡萄糖重吸收最主要的转运体。选择性的SGLT2抑制剂已成为治疗T2DM患者的新一类降糖药,通过促进尿葡萄糖和钠排泄,SGLT2抑制剂可降低血糖、血压。同时可改善Ins分泌及敏感性,降低糖毒性,改善T2DM患者的血流动力学变化,减少心血管事件及延缓DKD进展。然而,其作为T2DM标准治疗的可行性及相关机制仍有待进一步研究。本文对生理状态及T2DM状态肾脏对血糖的调控及SGLT2抑制剂对机体的治疗效应进行综述。
With the deep research of the pathogenesis of diabetes mellitus,the role of kidney in glucose homeostasis attracts more and more attention.In physiological status,kidney regulation on glucose metabolism includes producing glucose through gluconeogenesis,using glucose as a metabolic fuel,and reabsorbing all filtered glucose through the sodium–glucose cotransporters SGLT1 and SGLT2 located in the proximal tubule,which plays an important role in maintaining glucose homeostasis.However,handling of glucose by the kidney is widely altered in type 2 diabetes mellitus(T2 DM):renal gluconeogenesis and renal glucose uptake are increased in both the fasting and postprandial states,and renal glucose reabsorption is increased.The sodium glucose cotransporter SGLT2 in the early proximal tubule is the major pathway for renal glucose reabsorption.Specific SGLT2 inhibitors are being developed as a novel agent of controlling hyperglycaemia in T2 DM.By promoting urinary glucose and sodium excretion,SGLT2 inhibitors lead to a reduction in plasma glucose and blood pressure levels.It also improves insulin secretion and sensitivity,ameliorates glucotoxicity and induces haemodynamic effects that lead to improved cardiovascular and renal outcomes in T2 DM patients.However,the feasibility of its use as standard treatment for T2 DM and its related mechanism still need to be further studied.In this review we examine the role of kidney in glucose homeostasis in the physiological status and T2 DM and therapeutic significance through SGLT2 inhibitors.
作者
刘倩伶
李雪梅
LIU Qianling;LI Xuemei(Department of Nephrology,Peking Union Medical College Hospital,Beijing 100730,China)
出处
《中国糖尿病杂志》
CAS
CSCD
北大核心
2021年第4期314-320,共7页
Chinese Journal of Diabetes
