AJP - Endocrinology and Metabolism, Vol 258, Issue 5 E850-E855, Copyright © 1990 by American Physiological Society
Validation of two-pool model for in vivo ketone body kinetics
J. W. Bailey, M. W. Haymond and J. M. Miles
Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905.
Previous studies have indicated that simultaneous infusions of two ketone
body tracers ([13C]acetoacetate and [14C]beta-hydroxybutyrate) provide
accurate estimates of exogenous ketone body inflow when an open two-pool
model is employed. In the present studies, net hepatic ketone body
production was determined from surgically placed arterial, portal venous,
and hepatic venous catheters in conscious diabetic (n = 6) and 4-day fasted
(n = 7) dogs. [13C]acetoacetate and [14C]beta-hydroxybutyrate were infused
simultaneously, and ketone body production was calculated from either
acetoacetate (AcAc) single-isotope data, beta-hydroxybutyrate (beta-OHB)
single-isotope data, the sum of individual fluxes, or the two-pool model.
In fasted animals, both the AcAc single-isotope calculation and the sum of
individual fluxes overestimated net hepatic production by approximately 50%
(P less than 0.05), whereas the beta-OHB single-isotope calculation and the
two-pool model gave accurate estimates. In the diabetic animals, the
beta-OHB single-isotope calculation underestimated net hepatic production
by approximately 30% (P less than 0.05). The sum of individual fluxes
overestimated net hepatic production by approximately 46% (P less than
0.05), whereas both the AcAc single-isotope calculation and the two-pool
model gave accurate estimates. In conclusion, single-isotope methods give
erroneous estimates of net hepatic production of ketone bodies. In
contrast, a two-pool model provided an accurate estimate of net hepatic
production and thus appears to be suitable for determination of ketone body
kinetics in humans.
