Quantifying the contribution of gluconeogenesis to glucose production in fasted human subjects using stable isotopes

The contribution of gluconeogenesis to glucose production is estimated from the enrichment of the H bound to C-5 of glucose relative to either that bo und to C-2 of glucose or the enrichment in body water on ingesting (H2O)-H- 2 in the fasted state. Contributions of all gluconeogenic substrates are in cluded in the estimate and the limitation of an uncertain precursor enrichm ent removed. The half-life of (H2O)-H-2 in body water precludes a repeat st udy for many weeks. Glycogen cycling could result in underestimation, but t here is evidence that glycogen cycling does not occur in liver in the faste d state. Gluconeogenesis has been estimated by mass-isotopomer-distribution analyses, usually by administering C-13-labelled glycerol. Underestimates emphasize the major limitation of the method, i.e. the need to assume a sin gle enrichment of the precursor pool. Estimates of gluconeogenesis from iso topomer distribution in arterial-blood glucose and lactate on infusing [U-C -13(6)] glucose are unreliable, as a proportion of the glucose is formed fr om glycerol and from amino acids not converted to glucose via pyruvate. Los s of label in the Krebs cycle and relying on enrichment of arterial-blood l actate as a measure of hepatic pyruvate further add to the uncertainty. Est imates of the rate of gluconeogenesis by NMR are obtained by subtraction of the rate of glycogenolysis determined by NMR from the rate of glucose prod uction. Estimates are then the mean rate for the period over which glycogen contents are measured. Technical considerations can limit the accuracy of analyses and result in overestimates.