Kidney: its impact on glucose homeostasis and hormonal regulation

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.