Isotopic measurement of glucose and lactate kinetics

A variety of isotopic tracers can be used to quantitate glucose kinetics in vivo. Using the standard approach to calculate the rate of appearance (Ra) of glucose from kinetic data, different rates of Ra glucose are obtained depending on the nature and position of the label in glucose. If total glucose production is considered to be all glycogen breakdown and gluconeogenesis, then that value can be calculated using the following stable isotopic tracers, or, in most cases their radioactive counterparts: 6, 6-2H-glucose; 1-13C, 6-13C; and U-13C-glucose. In the case of the 13C-labeled glucose, account must be taken of the extent of recycling of labeled carbons. If U-13C-glucose is used and recycling of isotope not quantitated, the resulting calculated value for Ra glucose will represent the rate of production from non-recycled carbons, plus some recycled carbons, due to potential dilution of 13C in the oxaloacetate pool and some loss of 13C in the PEPCK reaction. Traditional calculation of Ra glucose using 2-2H-glucose will include the rate of total glucose production and the contribution from the glucose cycle, and use of 3-2H-glucose will include the rate of total glucose production and contribution of the fructose cycle. The traditional methodology used to measure lactate production, in contrast to glucose, has a major conceptual flaw. It requires the assumption that there is no isotopic exchange between lactate and other compounds, yet experimental evidence indicates that lactate and pyruvate are in rapid equilibrium. Consequently, this approach will overestimate the true rate of net lactate production, possibly by as much as 400%.