Measurement of gluconeogenesis and intermediary metabolism using stable isotopes
AssigneeBoard of Regents, The University of Texas System
InventorsCraig R. Malloy, A. Dean Sherry, John G. Jones
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Abstract
The present invention provides a combination of carbon-13 and deuterium metabolic tracers and methods that when used in conjuction with nuclear manegtic resonance spectroscopy, provide a measurement of metabolic fluxes in the target organisms. The tracers of the present invention may be taken orally during the same clinical exam. The metabolic information can be derived from blood, urine or other fluids to provide a comprehensive profile of glucogenic metabolism. The subject matter of the present invention may be applied to the study of metabolic dysfunction related to obesity, diabetes, HIV infection and a variety of other disease conditions.
Claims58
A method for preparing an tracer composition comprising:
- obtaining a 13C labeled Krebs cycle metabolite precursor that will produce an analyte;
- obtaining a deuterium source;
- wherein gluconeogenensis is measured from a subject that was provided the precursor and the deuterium source, and produced the analyte, by comparison of the relative nuclear magnetic resonance profiles of the labeled components in the analyte.
A method for preparing an tracer composition comprising:
- obtaining a deuterium source;
- wherein gluconeogenensis is measured from a subject that was provided the deuterium source, and produced an analyte, by comparison of the relative nuclear magnetic resonance profiles of the deuterium components in the analyte.
A method for preparing an isotopic metabolic flux tracer composition comprising:
- providing a 13C labeled Krebs cycle metabolite precursor to a subject to prouce an analyte;
- obtaining a sample from the subject;
- and
- measuring the nuclear magnetic resonance of the labeled tracers to determine the rate of gluconeogenesis.
A method for measuring metabolic flux in a sample using an isotopic metabolic flux tracer composition comprising:
- providing the sample with a 13C Krebs cycle precursor, D2O and acetaminophen;
- obtaining an analyte from the sample;
- and
- measuring the relative amounts of acetaminophen glucuronide and phenylacetylglutamine in the analyte using nuclear magnetic resonance.
A reagent kit for use in effecting a simultaneous assay for gluconeogenesis in a sample, said reagent kit comprising:
- a 13C labeled Krebs cycle precusor;
- and
- a labeled water tracer.
A method for determining gluconeogenesis comprising the steps of:
- providing a patient with a 13C labeled Krebs cycle precursor and D2O;
- obtaining a sample a blood, urine or tissue sample from the patient;
- measuring the 2H signal nuclear magnetic resonance spectra;
- measuring the 1H NMR nuclear magnetic resonance spectra;
- measuring the 13C—carbon nuclear magnetic resonance spectra;
- and
- calculating the rate of gluconeogenesis by taking the known infusion rate of a 13C radiolabelled Krebs cycle metabolite divided by the average fraction found in the sample over a predetermined period.
Dependencies are inferred from the claim text.