Department of Clinical Therapeutics, Athens University Medical School, Athens, Greece.
Diabetes Res Clin Pract. 2011 Aug;93 Suppl 1:S66-72. doi: 10.1016/S0168-8227(11)70016-X.
According to current textbook wisdom the liver is the exclusive site of glucose production in humans in the postabsorptive state. Although animal and in vitro studies have documented that the kidney is capable of gluconeogenesis, glucose production by the human kidney has been regarded as negligible. This knowledge is based on net balance measurements across the kidney. Recent studies combining isotopic and balance techniques have demonstrated that the human kidney is involved in the regulation of glucose homeostasis by making glucose via gluconeogenesis, taking up glucose from the circulation, and by reabsorbing glucose from the glomerular filtrate. The human liver and kidneys release approximately equal amounts of glucose via gluconeogenesis in the postabsorptive state. In the postprandial state, although overall endogenous glucose release decreases substantially, renal gluconeogenesis actually increases by approximately 2-fold. Following meal ingestion, glucose utilization by the kidney increases. Increased glucose uptake into the kidney may be implicated in diabetic nephropathy. Normally each day, ∼ 180 g of glucose is filtered by the kidneys; almost all of this is reabsorbed by means of sodium glucose cotransporter 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 begins to appear in the urine. Renal glucose release is stimulated by epinephrine and is inhibited by insulin. 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 postabsorptive and postprandial states, and renal glucose reabsorption is also increased Since renal glucose release is almost exclusively due to gluconeogenesis, it seems that the kidney is as important gluconeogenic organ as the liver. The most important renal gluconeogenic precursors appear to be lactae glutamine and glycerol.
根据目前的教科书知识，人类在吸收后状态下肝脏是葡萄糖生成的唯一部位。尽管动物和体外研究已经证明肾脏能够进行糖异生，但人类肾脏的葡萄糖生成一直被认为可以忽略不计。这种知识是基于肾脏的净平衡测量。最近的研究结合同位素和平衡技术表明，人类肾脏通过糖异生生成葡萄糖、从循环中摄取葡萄糖以及从肾小球滤液中重吸收葡萄糖来参与葡萄糖稳态的调节。人类肝脏和肾脏在吸收后状态下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，但肾脏糖异生实际上增加了约 2 倍。进食后，肾脏葡萄糖利用增加。肾脏葡萄糖摄取的增加可能与糖尿病肾病有关。正常情况下，每天约有 180 克葡萄糖被肾脏过滤；几乎所有这些都通过在近端小管中表达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，葡萄糖开始出现在尿液中。肾上腺素刺激肾脏葡萄糖释放，胰岛素抑制肾脏葡萄糖释放。2 型糖尿病（T2DM）中肾脏对葡萄糖的处理发生改变：吸收后和餐后状态下肾脏糖异生和肾脏葡萄糖摄取增加，肾脏葡萄糖重吸收也增加。由于肾脏葡萄糖释放几乎完全是由于糖异生，因此肾脏似乎是与肝脏一样重要的糖异生器官。最重要的肾脏糖异生前体似乎是乳清酸和甘油。
