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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, similar to 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. (C) 2011 Elsevier
Ireland Ltd. All rights reserved.
(EN)
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