Use of [3-³H]glucose and [6-¹⁴C]glucose to measure glucose turnover and glucose metabolism in humans

[3-³H]glucose is frequently used to measure glucose turnover in humans. If fructose 6-phosphate-fructose 1,6-diphosphate cycling (Fpc) is negligible in both liver and muscle, then [3-³H]- and [6-¹⁴C]glucose (corrected for Cori cycle activity) should provide equivalent measures of glucose turnover. In addition, if glycogenolysis is fully suppressed, then [¹⁴C]lactate specific activity should equal that of [6-¹⁴C]glucose from which it was derived, and oxidation of [6-¹⁴C]glucose, as measured by rate of generation of ¹⁴CO₂, should equal total glucose oxidation (i.e., that derived from intra- and extracellular pools) as measured by indirect calorimetry. To address these questions, glucose turnover was measured simultaneously with [3-³H]- and [6-¹⁴C]glucose in the basal state and in presence of low (~200 pM) and high (~750 pM) insulin concentrations. Glucose turnover rates measured with [3-³H]- and [6-¹⁴C]glucose were equivalent at all insulin concentrations, indicating that Fpc had no detectable effect on measurement of glucose appearance. [¹⁴C]lactate specific activity was lower (P < 0.01) than that of [6-¹⁴C]glucose in the basal state but not during either low- or high-dose insulin infusion, implying that all lactate was derived from extracellular glucose. On the other hand, glucose oxidation as measured by rate of generation of ¹⁴CO₂ was lower (P < 0.05) than glucose oxidation as measured by indirect calorimetry during both insulin infusions, implying either that suppression of glycogenolysis was not complete in all tissues or that one or both of these techniques do not accurately measure glucose oxidation. We conclude that, at insulin concentrations within physiological range, 1) Fpc has no detectable effect on measurement of glucose turnover with [3-³H]glucose, and 2) at insulin concentrations ranging from 200 to 800 pM, lactate is exclusively derived from extracellular glucose.