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Departments of 1 Medicine and Physiology and 2 Pharmacology, University of Rochester School of Medicine, Rochester, New York 14642; and 3 Department of Pediatrics, Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas 77030
Release of glucose by the kidney in
postabsorptive normal humans is generally regarded as being wholly due
to gluconeogenesis. Although lactate is the most important systemic
gluconeogenic precursor and there is appreciable net renal lactate
uptake, renal lactate gluconeogenesis has not yet been investigated.
The present studies were therefore undertaken to quantitate the
contribution of lactate to renal gluconeogenesis and the role of the
kidney in lactate metabolism. We determined systemic and renal lactate conversion to glucose as well as renal lactate net balance, fractional extraction, uptake, and release in 24 postabsorptive humans by use of a
combination of isotopic and renal balance techniques. For comparative
purposes, accumulated similar data for glutamine, alanine, and glycerol
are also reported. Systemic lactate gluconeogenesis (1.97 ± 0.12 µmol · kg
1 · min1) was
about threefold greater than that from glycerol, glutamine, and
alanine. The sum of gluconeogenesis from these precursors, uncorrected
for tricarboxylic acid (TCA) cycle carbon exchange, explained
34% of systemic glucose release. Renal lactate uptake (3.33 ± 0.28 µmol · kg1 · min1)
accounted for nearly 30% of its systemic turnover. Renal
gluconeogenesis from lactate (0.78 ± 0.10 µmol · kg1 · min1) was
3.5, 2.5, and 9.6-fold greater than that from glycerol, glutamine, and
alanine. The sum of renal gluconeogenesis from these precursors equaled
~40% of the sum of their systemic gluconeogenesis. When the
isotopically determined rates of systemic and renal gluconeogenesis were corrected for TCA cycle carbon exchange, gluconeogenesis from
these precursors accounted for 43% of systemic glucose release and
89% of renal glucose release. We conclude that 1) in
postabsorptive normal humans, lactate is the dominant precursor for
both renal and systemic gluconeogenesis; 2) the kidney is an
important organ for lactate disposal; 3) under these
conditions, renal glucose release is predominantly, if not exclusively,
due to gluconeogenesis; and 4) liver and kidney are
similarly important for systemic gluconeogenesis.
glutamine; alanine; glycerol; lactate; kidney
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