Glucose production, gluconeogenesis, and hepatic tricarboxylic acid cycle fluxes measured by nuclear magnetic resonance analysis of a single glucose derivative

A triple-tracer method was developed to provide absolute fluxes contributing to endogenous glucose production and hepatic tricarboxylic acid (TCA) cycle fluxes in 24-h-fasted rats by H-2 and C-13 nuclear magnetic resonance (NMR) analysis of a single glucose derivative. A primed, intravenous [3,4-C-13(2)] glucose infusion was used to measure endogenous glucose production; intraperitoneal (H2O)-H-2 (to enrich total body water) was used to quantify sources of glucose (TCA cycle, glycerol, and glycogen), and intraperitoneal [U-C-13(3)] propionate was used to quantify hepatic anaplerosis, pyruvate cycling, and TCA cycle flux. Plasma glucose was converted to monoacetone glucose (MAG), and a single H-2 and C-13 NMR spectrum of MAG provided the following metabolic data (all in units of mumol/kg/min; n = 6): endogenous glucose production (40.4 +/- 2.9), gluconeogenesis from glycerol (11.5 +/- 3.5), gluconeogenesis from the TCA cycle (67.3 +/- 5.6), glycogenolysis (1.0 +/- 0.8), pyruvate cycling (154.4 +/- 43.4), PEPCK flux (221.7 +/- 47.6), and TCA cycle flux (49.1 +/- 16.8). In a separate group of rats, glucose production was not different in the absence of (H2O)-H-2 and [U-C-13]propionate, demonstrating that these tracers do not alter the measurement of glucose turnover. (C) 2004 Elsevier Inc. All rights reserved.