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 conjunction with nuclear magnetic 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.
Claims31
A method for preparing a tracer composition comprising:
- obtaining a 13C labeled Krebs cycle metabolite precursor that will produce an analyte;
- and
- obtaining a deuterium source,
- wherein gluconeogenesis is measured from a subject that was provided the precursor and the deuterium source, and produced the analyte, by comparison of relative nuclear magnetic resonance signal areas in a spectrum obtained from labeled components in the analyte.
A method for preparing a tracer composition comprising:
- obtaining a deuterium source,
- wherein gluconeogenesis is measured from a subject that was provided the deuterium source, and produced an analyte, by comparison of the relative nuclear magnetic resonance signal areas in a spectrum obtained from deuterium components in the analyte, wherein the analyte is selected from the group consisting of glucose deuterated in the 2, 5 and 6 positions and deuterated glucose with any transformation that maintains the 2,5 and 6 positions in relation to one another.
A method for preparing a tracer composition comprising:
- obtaining a deuterium source,
- wherein gluconeogenesis is measured from a subject that was provided the deuterium source, and produced an analyte, by comparison of the relative nuclear magnetic resonance signal areas in a spectrum obtained from deuterium components in the analyte, wherein the analyte is (1-613C2).glucose.
A method for preparing a tracer composition comprising:
- obtaining a deuterium source;
- wherein gluconeogenesis is measured from a subject that was provided the deuterium source, and produced an analyte, by comparison of the relative nuclear magnetic resonance signal areas in a spectrum obtained from deuterium components in the analyte, wherein the analyte is selected from the group consisting of pyruvic acid, acetic acid citric acid, isocitric acid, cis-aconitic acid, 2-ketoglutaric acid, succinic acid, fumaric acid, malic acid, oxaloacetic acid, and mixtures thereof.
A method for preparing an isotopic metabolic flux tracer composition comprising:
- providing a 13C labeled Krebs cycle metabolite precursor to a subject to produce an analyte;
- obtaining a sample from the subject;
- and
- measuring nuclear magnetic resonance signals of the sample to determine the rate of gluconeogenesis.
A method for preparing a tracer composition comprising:
- obtaining a deuterium source;
- wherein gluconeogenesis is measured from a subject that was provided the deuterium source, and produced an analyte, by comparison of the relative nuclear magnetic resonance signal areas in a spectrum obtained from deuterium components in the analyte, and
- wherein the analyte is glucose deuterated in the 2, 5 and 6 positions, and any transformation of glucose that maintains the 2,5 and 6 positions in relation to one another, and
- wherein the analyte is produced in the blood, urine or tissue.
A method for preparing an isotopic metabolic flux tracer composition comprising:
- providing a 13C labeled Krebs cycle metabolite precursor to a subject to produce an analyte;
- obtaining a sample from the subject;
- and
- measuring nuclear magnetic resonance of labeled tracers in the sample to determine the rate of gluconeogenesis,
- wherein the analyte is 13C-glucose.
Dependencies are inferred from the claim text.