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Am J Physiol Endocrinol Metab 284: E1162-E1171, 2003. First published February 25, 2003; doi:10.1152/ajpendo.00425.2002
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Vol. 284, Issue 6, E1162-E1171, June 2003

Gluconeogenesis in humans with induced hyperlactatemia during low-intensity exercise

Mark J. Roef1, Kees de Meer1,2, Satish C. Kalhan3, Helma Straver4, Ruud Berger4, and Dirk-Jan Reijngoud5

1 Departments of Pediatric Gastroenterology and 2 Clinical Chemistry and Pediatrics, VU University Medical Center, 1007 MB Amsterdam; 4 Laboratory for Metabolic Diseases, University Children's Hospital, 3508 AB Utrecht; and 5 Laboratory for Metabolic Diseases, Department of Pediatrics, University Hospital Groningen, 9700 RB Groningen, The Netherlands; and 3 Robert Schwartz, M.D., Center for Metabolism and Nutrition, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109

We studied the role of lactate in gluconeogenesis (GNG) during exercise in untrained fasting humans. During the final hour of a 4-h cycle exercise at 33-34% maximal O2 uptake, seven subjects received, in random order, either a sodium lactate infusion (60 µmol · kg-1 · min-1) or an isomolar sodium bicarbonate infusion. The contribution of lactate to gluconeogenic glucose was quantified by measuring 2H incorporation into glucose after body water was labeled with deuterium oxide, and glucose rate of appearance (Ra) was measured by [6,6-2H2]glucose dilution. Infusion of lactate increased lactate concentration to 4.4 ± 0.6 mM (mean ± SE). Exercise induced a decrease in blood glucose concentration from 5.0 ± 0.2 to 4.2 ± 0.3 mM (P < 0.05); lactate infusion abolished this decrease (5.0 ± 0.3 mM; P < 0.001) and increased glucose Ra compared with bicarbonate infusion (P < 0.05). Lactate infusion increased both GNG from lactate (29 ± 4 to 46 ± 4% of glucose Ra, P < 0.001) and total GNG. We conclude that lactate infusion during low-intensity exercise in fasting humans 1) increased GNG from lactate and 2) increased glucose production, thus increasing the blood glucose concentration. These results indicate that GNG capacity is available in humans after an overnight fast and can be used to sustain blood glucose levels during low-intensity exercise when lactate, a known precursor of GNG, is available at elevated plasma levels.

lactate; hyperlactatemia; stable isotopes


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