Diabetes, Vol 49, Issue 7 1186-1193, Copyright © 2000 by American Diabetes Association

ARTICLES

Renal substrate metabolism and gluconeogenesis during hypoglycemia in humans

E Cersosimo, P Garlick and J Ferretti
Department of Medicine, State University of New York at Stony Brook, 11794-8154, USA. ecersosi@mail.som.sunysb.edu

To examine the potential contribution of precursor substrates to renal gluconeogenesis during hypoglycemia, 14 healthy subjects had arterialized hand vein and renal vein (under fluoroscopy) catheterized after an overnight fast. Net renal balance of lactate, glycerol, alanine, and glutamine was determined simultaneously with systemic and renal glucose kinetics using arteriovenous concentration differences and 6-[2H2]glucose tracer dilution. Renal plasma flow was measured by para-aminohippurate clearance and was converted to blood flow using the mathematical value (1-hematocrit). Arterial and renal vein samples were obtained in the postabsorptive state and during a 180-min hyperinsulinemic period during either euglycemia or hypoglycemia. Insulin increased from 49 +/- 14 to 130 +/- 25 pmol/l (hypoglycemia) and to 102 +/- 10 pmol/l (euglycemia). Arterial blood glucose decreased from 4.5 +/-0.2 to 3.0 +/- 0.1 mmol/l during hypoglycemia but did not change during euglycemia (4.3 +/- 0.2 mmol/l). After 150 min, endogenous glucose production reached a plateau value that was higher during hypoglycemia (10.3 +/0.6 micromol x kg(-1) x min(-1)) than during euglycemia (5.73 +/-0.6 micromol x kg(-1) x min(-1), P < 0.001). Hypoglycemia was associated with a rise in renal glucose production (RGP) from 3.0 +/- 0.7 to 5.4 +/- 0.6 micromol x kg(-1) x min(-1) (P < 0.05), although glucose utilization remained the same (2.0 +/- 0.8 vs. 2.1 +/-0.6 micromol x kg(-1) x min(-1)). As a result, net renal glucose output increased from 1.0 +/- 0.3 to 3.3 +/- 0.40 micromol x kg(-1) x min(-1). Elevations in net renal uptake of lactate (2.4 +/- 0.5 to 3.5 +/- 0.7 vs. 2.8 +/- 0.4 micromol x kg(-1) x min(-1)), glycerol (0.6 +/- 0.3 to 1.3 +/- 0.5 vs. 0.4 +/- 0.2 micromol x kg(-1) x min(-1)), and glutamine (0.7 +/- 0.2 to 1.1 +/- 0.3 vs. 0.1 +/- 0.3 micromol x kg(-1) x min(-1)) during hypoglycemia versus euglycemia (P < 0.05) could account for nearly 60% of all glucose carbons released in the renal vein during hypoglycemia. Our data indicate that extraction of circulating gluconeogenic precursors by the kidney is enhanced and responsible for a substantial fraction of the compensatory rise in RGP during sustained hypoglycemia. Increased renal gluconeogenesis from circulating substrates represents an additional physiological mechanism by which the decrease in blood glucose concentration is attenuated in humans.
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