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Am J Physiol Endocrinol Metab 275: E717-E728, 1998;
0193-1849/98 $5.00
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Vol. 275, Issue 4, E717-E728, October 1998

MODELING IN PHYSIOLOGY
Simultaneous time-varying systemic appearance of oral and hepatic glucose in adults monitored with stable isotopes

G. Livesey1, P. D. G. Wilson2, J. R. Dainty2, J. C. Brown1, R. M. Faulks1, M. A. Roe1, T. A. Newman1, J. Eagles1, F. A. Mellon1, and R. H. Greenwood3

Departments of 1 Nutrition, Diet, and Health and of 2 Food Biophysics, Institute of Food Research, Norwich NR4 7UA; and 3 Department of Medicine, Norfolk and Norwich Hospital, Norwich NR1 3SR, United Kingdom

The rates (and extent) of appearance of glucose in arterialized plasma from an oral glucose load and from liver (RaO, RaH) can be estimated in humans using radioisotopes, but estimates vary among laboratories. We investigated the use of stable isotopes and undertook 22 primed intravenous infusions of D-[6,6-2H2]glucose with an oral load including D-[13C6]glucose in healthy humans. The effective glucose pool volume (VS) had a lower limit of 230 ml/kg body weight (cf. 130 ml/kg commonly assumed). This VS in Steele's one-compartment model of glucose kinetics gave a systemic appearance from a 50-g oral glucose load per 70 kg body weight of 96 ± 3% of that ingested, which compared with a theoretical value of ~95%. Mari's two-compartment model gave 100 ± 3%. The two models gave practically identical RaO and RaH at each point in time and a plateau in the cumulative RaO when absorption was complete. Less than 3% of 13C was recycled to [13C3]glucose, suggesting that recycling errors were practically negligible in this study. Causes of variation among laboratories are identified. We conclude that stable isotopes provide a reliable and safe alternative to radioactive isotopes in these studies.

metabolism; absorption; hepatic production; modeling


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