MEASUREMENT OF HEPATIC GLUCOSE OUTPUT, KREBS CYCLE, AND GLUCONEOGENICFLUXES BY NMR ANALYSIS OF A SINGLE PLASMA-GLUCOSE SAMPLE

C-13 and H-1 NMR spectroscopy of plasma glucose was used to resolve th e isotopomer contributions from tracer levels of [1,6-C-13(2)]glucose, a novel tracer of glucose carbon skeleton turnover, and [U-C-13]propi onate, a tracer of hepatic citric acid cycle metabolism. This allowed simultaneous measurements of hepatic glucose production and citric aci d cycle fluxes from the NMR analysis of a single plasma glucose sample in fasted animals. Glucose carbon skeleton turnover, as reported by t he dilution of [1,6-C-13(2),]glucose, was 56 +/- 2 mu mol/kg/min in th e presence of labeling from [U-C-13]propionate and 53 +/- 4 mu mol/kg/ min in its absence. Therefore, as expected, the labeling contributions from [U-C-13]propionate metabolism did not have a significant effect on the measurement of glucose turnover. For the group infused with bot h tracers, citric acid cycle flux estimates from the analysis of gluco se C2 isotopomer ratios were consistent with those from our recent exp eriments where only [U-C-13]propionate was infused, verifying that the presence of [1,6-C-13(2)]glucose did not interfere with these measure ments, This integrated analysis of hepatic glucose output and citric a cid cycle fluxes from plasma glucose isotopomers yielded a noninvasive estimate of hepatic citrate synthase flux of 74 +/- 12 mu mol/kg/min for 24-h fasted rats. (C) 1998 Academic Press.