胰高血糖素样肽-1受体激动剂和钠葡萄糖共转运体-2抑制剂的中枢神经系统靶点

Central nervous system targets of glucagon-like peptide-1 receptor agonist and sodium-glucose cotransporter-2 inhibitor

肥胖是2型糖尿病形成最主要的病因,而慢性心衰是2型糖尿病主要的致死原因。在高等哺乳动物中,中枢神经系统通过各种神经内分泌途径调节进食行为和体重,控制着能量代谢相关的各种生理过程。已有很多研究证明肥胖发生、发展与中枢神经内分泌调节障碍有关。另外,很多研究证实,早期2型糖尿病可以通过饮食、运动及药物进行缓解。干预肥胖可以延缓2型糖尿病的发生和并发症的出现。目前内分泌科常用的新药胰高血糖素样肽1受体激动剂(glucagon-like peptide-1 receptor agonist,GLP-1RA)和钠葡萄糖共转运体-2抑制剂(so⁃dium glucose co-transportor-2 inhibitor,SGLT-2i)被发现可以改善肥胖和心血管并发症。GLP-1RA可以减少糖尿病病人26%的心血管并发症;SGLT2i可以减少糖尿病病人30%的慢性心衰发生。但目前,仍然有两个问题困扰着临床医师:1.GLP-1RA是否可以通过血脑屏障(blood-brain-barrier,BBB),并在哪些核团控制饮食和能量平衡。2.SGLT2i是否可以通过BBB并抑制过度激活的交感神经系统,进而起到降低心率、抑制慢性心衰的作用。故本文就这两种药物控制饮食和减少心衰可能的中枢神经系统通路和机制做一总结。

Obesity is the primary cause of type 2 diabetes(T2D);Diabetes-related chronic heart failure is also a fatal complica⁃tion of T2D.The central nervous system regulates feeding behavior and body weight in mammals via several neuroendocrine pathways,as well as many physiological processes related to energy consumption.Numerous studies have linked obesity's onset and progression to endocrine regulation disorders in the central nervous system.As a result,diabetic remission can be achieved in the early onset of T2D using a combination of diet,exercise,and medications.Obesity intervention can delay type 2 diabetes onset and complications.New an⁃tidiabetic drugs frequently used in endocrinology,such as glucagon-like peptide-1 receptor agonist(GLP-1RA)and sodium-glucose cotransporter-2 inhibitor(SGLT-2i),have been observed to improve obesity and cardiovascular issues.GLP-1RA could reduce 26%of the cardiovascular complication;SGLT2i can reduce chronic heart failure by 30%in diabetic patients.There are two questions still puzzle clinicians:1.Whether GLP-1RA transport can across the blood-brain barrier(BBB),and in which nuclei does it control diet and energy balance?2.Whether SGLT2i can transport across the BBB and inhibit the over-activated sympathetic nervous system,thereby reducing heart rate and inhibiting chronic heart failure?Therefore,this article summarizes the possible central nervous system path⁃ways and mechanisms of these two drugs to control diet and reduce heart failure.