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.