Validation of two-pool model for in vivo ketone body kinetics.
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.
Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905.
J W
JW
Bailey
M W
MW
Haymond
J M
JM
Miles
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000378:metabolism; D000818:Animals; D002247:Carbon Isotopes; D002250:Carbon Radioisotopes; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D004285:Dogs; D005215:Fasting; D006885:Hydroxybutyrates / Q000378:metabolism; D007328:Insulin / Q000627:therapeutic use; D007657:Ketone Bodies / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D008433:Mathematics; D008954:Models, Biological; D010180:Pancreatectomy; D012016:Reference Values
D000090:Acetoacetates; D002247:Carbon Isotopes; D002250:Carbon Radioisotopes; D006885:Hydroxybutyrates; D007328:Insulin; D007657:Ketone Bodies; C016635:acetoacetic acid; D020155:3-Hydroxybutyric Acid