Determination of Krebs cycle metabolic carbon exchange in vivo and its use to estimate the individual contributions of gluconeogenesis and glycogenolysis to overall glucose output in man

Journal Article · Sun Nov 01 04:00:00 EST 1987 · J. Clin. Invest.; (United States)

DOI:https://doi.org/10.1172/JCI113206· OSTI ID:5652869

Consoli, A; Kennedy, F; Miles, J; Gerich, J

Current isotopic approaches underestimate gluconeogenesis in vivo because of Krebs cycle carbon exchange and the inability to measure intramitochondrial precursor specific activity. We therefore applied a new isotopic approach that theoretically overcomes these limitations and permits quantification of Krebs cycle carbon exchange and the individual contributions of gluconeogenesis and glycogenolysis to overall glucose outputex. (6-3H)Glucose was infused to measure overall glucose output; (2-14C)acetate was infused to trace phosphoenolpyruvate gluconeogenesis and to calculate Krebs cycle carbon exchange as proposed by Katz. Plasma (14C)3-OH-butyrate specific activity was used to estimate intramitochondrial acetyl coenzyme A (CoA) specific activity, and finally the ratio between plasma glucose 14C-specific activity and the calculated intracellular phosphoenolpyruvate 14C-specific activity was used to determine the relative contributions of gluconeogenesis and glycogenolysis to overall glucose output. Using this approach, acetyl CoA was found to enter the Krebs cycle at twice (postabsorptive subjects) and three times (2 1/2-d fasted subjects) the rate of pyruvate, respectively. Gluconeogenesis in postabsorptive subjects (3.36 +/- 0.20 mumol/kg per min) accounted for 28 +/- 2% of overall glucose output and increased twofold in subjects fasted for 2 1/2-d (P less than 0.01), accounting for greater than 97% of overall glucose output. Glycogenolysis in postabsorptive subjects averaged 8.96 +/- 0.40 mumol/kg per min and decreased to 0.34 +/- 0.08 mumol/kg per min (P less than 0.01) after a 2 1/2-d fast. Since these results agree well with previously reported values for gluconeogenesis and glycogenolysis based on determinations of splanchnic substrate balance and glycogen content of serial liver biopsies.

• Research Organization: Univ. of Pittsburgh, School of Medicine, PA
• OSTI ID: 5652869
• Journal Information: J. Clin. Invest.; (United States), Journal Name: J. Clin. Invest.; (United States) Vol. 80:5; ISSN JCINA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETATES
ALDEHYDES
BUTYRIC ACID
CARBOHYDRATES
CARBON
CARBON 14 COMPOUNDS
CARBOXYLIC ACID SALTS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
ELEMENTS
FASTING
GLUCOSE
GLYCOGEN
HEXOSES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
METABOLISM
MITOCHONDRIA
MONOCARBOXYLIC ACIDS
MONOSACCHARIDES
NONMETALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANOIDS
PHOSPHOENOLPYRUVATE
POLYSACCHARIDES
SACCHARIDES
TRACER TECHNIQUES
TRITIUM COMPOUNDS