Stable Isotope Techniques for the Study of Gluconeogenesis in Man

Glucose is produced by gluconeogenesis from pyruvate and its precursors and from glycerol and by glycogenolysis (Fig. 1). We introduced a technique using ²H₂O to quantitate the contribution of gluconeogenesis to glucose production in the fasted state (1,2). The method removes the uncertainty in older methods using radioactive or stable isotopes of knowing 1) the enrichment or specific activity of the gluconeogenic precursor being traced, 2) the contribution to gluconeogenesis of that precursor compared to contributions by the other precursors, and 3) the extent of dilution of label of that precursor in the Krebs cycle during the course of its conversion to glucose.