Journal of Glycobiology
Open Access

Use of stable isotope tracers and chemical biopsy methods for non-invasive studies of hepatic carbohydrate metabolism in humans

Glycobiology World Congress

August 10-12, 2015 Philadelphia, USA

John Griffith Jones

Posters-Accepted Abstracts: J Glycobiol

Abstract :

The liver plays a central role in the maintenance of constant blood glucose levels during the daily feeding-fasting cycle. This
is achieved by a coordinated reciprocal regulation of metabolic pathways that generate glucose such as gluconeogenesis
and glycogenolysis and pathways that dispose of glucose such as glycolysis, glycogenesis and lipogenesis. In diseases such as
diabetes and glycogen storage disease, this regulation is disrupted resulting in unstable blood glucose levels. To more precisely
understand how these pathologies disrupt the control of hepatic glucose fluxes in humans, there is a need for practical, safe and
non-invasive methods for evaluating hepatic carbohydrate fluxes. To this end, we are developing non-invasive measurements
of these fluxes using deuterated water (2H2O) as a relatively inexpensive and easily administered isotopic tracer coupled
with â�?�?Chemical Biopsyâ�? of UDP-glucose via glucuronidation of Acetaminophen and other xenobiotic compounds whose
glucuronides are cleared into urine. Analysis of urinary glucuronide positional 2H-enrichment by high-resolution 2H NMR
informs the main sources of endogenous glucose and glycogen synthesis. Integration of this information with 13C NMR
measurements of glucose and glucuronide 13C-isotopomers from 13C-enriched precursors provides further detail on the
metabolism of specific sugars or gluconeogenic substrates. To illustrate the application of NMR and stable isotope tracers
in improving our understanding of hepatic carbohydrate metabolism, highlights of our studies will be presented and future
perspectives will be briefly discussed.