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Am J Physiol Endocrinol Metab (February 25, 2003). doi:10.1152/ajpendo.00425.2002
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Submitted on October 2, 2002
Accepted on February 13, 2003

Gluconeogenesis in humans with induced hyperlactatemia during low-intensity exercise

Mark J. Roef1, Kees De Meer2*, Satish C. Kalhan3, Helma Straver4, Ruud Berger4, and Dirk-Jan Reijngoud5

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

* To whom correspondence should be addressed. E-mail: novosilski{at}hotmail.com.

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 % VO2max seven subjects received either a sodium lactate infusion (60 µmol.kg-1min-1) or an isomolar sodium bicarbonate infusion, in random order. The contribution of lactate to gluconeogenic glucose was quantified by measuring [2H] incorporation into glucose after labeling body water with deuteriumoxide, 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 mM 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 when compared to 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 gluconeogenesis 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.




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