University of Rochester School of Medicine, Rochester, NY 14642, USA.
Diabet Med. 2010 Feb;27(2):136-42. doi: 10.1111/j.1464-5491.2009.02894.x.
Considerable data have accumulated over the past 20 years, indicating that the human kidney is involved in the regulation of glucose via gluconeogenesis, taking up glucose from the circulation, and by reabsorbing glucose from the glomerular filtrate. In light of the development of glucose-lowering drugs involving inhibition of renal glucose reabsorption, this review summarizes these data. Medline was searched from 1989 to present using the terms 'renal gluconeogenesis', 'renal glucose utilization', 'diabetes mellitus' and 'glucose transporters'. The human liver and kidneys release approximately equal amounts of glucose via gluconeogenesis in the post-absorptive state. In the postprandial state, although overall endogenous glucose release decreases substantially, renal gluconeogenesis increases by approximately twofold. Glucose utilization by the kidneys after an overnight fast accounts for approximately 10% of glucose utilized by the body. Following a meal, glucose utilization by the kidney increases. Normally each day, approximately 180 g of glucose is filtered by the kidneys; almost all of this is reabsorbed by means of sodium-glucose co-transporter 2 (SGLT2), expressed in the proximal tubules. However, the capacity of SGLT2 to reabsorb glucose from the renal tubules is finite and, when plasma glucose concentrations exceed a threshold, glucose appears in the urine. Handling of glucose by the kidney is altered in Type 2 diabetes mellitus (T2DM): renal gluconeogenesis and renal glucose uptake are increased in both the post-absorptive and postprandial states, and renal glucose reabsorption is increased. Specific SGLT2 inhibitors are being developed as a novel means of controlling hyperglycaemia in T2DM.
在过去的 20 年中积累了相当多的数据，这些数据表明人类肾脏通过糖异生、从循环中摄取葡萄糖以及从肾小球滤过液中重吸收葡萄糖来参与葡萄糖的调节。鉴于涉及抑制肾脏葡萄糖重吸收的降血糖药物的发展，本综述总结了这些数据。使用“肾糖异生”、“肾葡萄糖利用”、“糖尿病”和“葡萄糖转运体”等术语，从 1989 年至今在 Medline 上进行了搜索。在吸收后状态下，人类肝脏和肾脏通过糖异生释放等量的葡萄糖。在餐后状态下，尽管整体内源性葡萄糖释放大量减少，但肾脏糖异生增加约两倍。在禁食过夜后，肾脏对葡萄糖的利用约占全身葡萄糖利用的 10%。进食后，肾脏对葡萄糖的利用增加。正常情况下，每天约有 180 克葡萄糖被肾脏过滤；几乎所有的葡萄糖都通过表达于近端肾小管的钠-葡萄糖协同转运蛋白 2（SGLT2）重吸收。然而，SGLT2 从肾小管重吸收葡萄糖的能力是有限的，当血浆葡萄糖浓度超过阈值时，葡萄糖就会出现在尿液中。2 型糖尿病（T2DM）患者肾脏对葡萄糖的处理发生改变：在吸收后和餐后状态下，肾脏糖异生和肾脏葡萄糖摄取均增加，并且肾脏葡萄糖重吸收增加。正在开发特定的 SGLT2 抑制剂作为控制 T2DM 高血糖的新方法。
