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.