Proceedings of the Nutrition Society

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


Bernard R. Landaua1 c1



a1 Departments of Medicine, Biochemistry, and Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH 44106–4951, USA

Article author query

Landau BR [PubMed]  [Google Scholar]

Abstract

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 bound to C-2 of glucose or the enrichment in body water on ingesting 2H2O in the fasted state. Contributions of all gluconeogenic substrates are included in the estimate and the limitation of an uncertain precursor enrichment removed. The half-life of 2H2O in body water precludes a repeat study for many weeks. Glycogen cycling could result in underestimation, but there is evidence that glycogen cycling does not occur in liver in the fasted state. Gluconeogenesis has been estimated by mass-isotopomer-distribution analyses, usually by administering 13C-labelled glycerol. Underestimates emphasize the major limitation of the method, i.e. the need to assume a single enrichment of the precursor pool. Estimates of gluconeogenesis from isotopomer distribution in arterial-blood glucose and lactate on infusing [U-13C6] glucose are unreliable, as a proportion of the glucose is formed from glycerol and from amino acids not converted to glucose via pyruvate. Loss of label in the Krebs cycle and relying on enrichment of arterial-blood lactate as a measure of hepatic pyruvate further add to the uncertainty. Estimates of the rate of gluconeogenesis by NMR are obtained by subtraction of the rate of glycogenolysis determined by NMR from the rate of glucose production. 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.

Key Words: 2H-labelled water; Gluconeogenesis; Stable isotopes; NMR; Mass-isotopomer analysis

Correspondence:

c1 Corresponding Author: Professor B. R. Landau, fax +1 216 368 4937, email epc2@po.cwru.edu