a–d, Time courses of plasma lactate concentrations (a), glucose concentration (in millimoles per liter) (b), plasma lactate 13C fractional enrichment (FE) (c), and glucose 13C fractional enrichment (d) from the same volunteer for the two different infusion protocols A (black symbols) and B (white symbols). As aimed, plasma lactate level is either (protocol A) maintained close to a physiological level (∼1.5 mmol/L) with a 13C FE close to 33% or (protocol B) doubled (∼2.5 mmol/L) with a 13C FE close to 50%. Even if the plasma glucose level remains steady at euglycemic values, as the circulating [3-13C]lactate is metabolized by the liver, 13C atoms are progressively incorporated into the plasma glucose through gluconeogenesis.