Validation of two-pool model for in vivo ketone body kinetics
- Mayo Clinic, Rochester, MN (USA)
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.
- OSTI ID:
- 6871107
- Journal Information:
- American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 258; ISSN 0002-9513; ISSN AJPHA
- Country of Publication:
- United States
- Language:
- English
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550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETOACETATES
ANIMALS
BIOSYNTHESIS
BODY
CARBON 13
CARBON 14 COMPOUNDS
CARBON ISOTOPES
CARBOXYLIC ACID SALTS
DIABETES MELLITUS
DIGESTIVE SYSTEM
DISEASES
DOGS
ENDOCRINE DISEASES
EVEN-ODD NUCLEI
FASTING
GLANDS
HORMONES
INSULIN
ISOTOPE APPLICATIONS
ISOTOPES
KETONES
LABELLED COMPOUNDS
LIGHT NUCLEI
LIVER
MAMMALS
MATHEMATICAL MODELS
METABOLIC DISEASES
NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
STABLE ISOTOPES
SYNTHESIS
TESTING
TRACER TECHNIQUES
VALIDATION
VERTEBRATES