Seinsheimer Cardiovascular Health Program, Medical University of South Carolina, Ralph H. Johnson VA Medical Center, Charleston, SC 29403, USA.
Postgrad Med. 2011 Jul;123(4):38-45. doi: 10.3810/pgm.2011.07.2302.
Hyperglycemia is a defining characteristic of type 2 diabetes mellitus and is a major risk factor associated with the development of many microvascular complications. There are numerous therapies currently available to treat hyperglycemia, but glycemic control rates remain poor. One potential reason is the decline in ß-cell function over time, which decreases the effectiveness of therapies that rely on insulin action. The kidney occupies a central position in the control of glucose homeostasis by its role in gluconeogenesis and by regulating glucose excretion. Under normal conditions, glucose filtered by the kidney is virtually totally reabsorbed in the proximal tubule by the sodium-glucose co-transporter 2 (SGLT2). Inhibition of SGLT2 is an attractive, insulin-independent target for increasing glucose excretion in the setting of hyperglycemia. A number of SGLT2 inhibitors have been synthesized, and results from preclinical studies have shown that they increase glucose excretion and normalize plasma glucose in diabetic models. Initial clinical data are promising and suggest that SGLT2 inhibitors may be a new therapeutic option for treating type 2 diabetes mellitus.
高血糖是 2 型糖尿病的一个特征，也是与许多微血管并发症发展相关的主要危险因素。目前有许多治疗高血糖的方法，但血糖控制率仍然很差。一个潜在的原因是随着时间的推移，β细胞功能下降，这降低了依赖胰岛素作用的治疗方法的有效性。肾脏通过其在糖异生中的作用以及调节葡萄糖排泄，在葡萄糖稳态的控制中占据中心位置。在正常情况下，肾脏滤过的葡萄糖几乎全部通过近端小管中的钠-葡萄糖协同转运蛋白 2（SGLT2）被重吸收。抑制 SGLT2 是增加高血糖时葡萄糖排泄的一种有吸引力的、不依赖胰岛素的靶点。已经合成了许多 SGLT2 抑制剂，临床前研究的结果表明，它们可增加葡萄糖排泄并使糖尿病模型中的血糖正常化。初步的临床数据很有希望，表明 SGLT2 抑制剂可能是治疗 2 型糖尿病的一种新的治疗选择。
