Direct administration and utilization of [1-13C]glucose by fetal brain and liver tissues under normal and ischemic conditions:1H,31P, and13C NMR studies

Abstract

Three distinct, maternal-independent routes (e.g. intraamniotic, intraperitoneal and intracerebral), for [1-13C]glucose utilization by fetal brain and liver tissues, were examined by multinuclear magnetic resonance (NMR) spectroscopy before and after vascular occlusion of the maternal-fetal blood flow. Labeled lactate was the major glycolytic product by all routes, but in addition labeled TCA cycle products were also generated. Fractional 13C enrichment in both glucose and lactate were always higher in the ischemic state compared to controls using either one of the three routes studied. After intraperitoneal injection total glucose in the fetal brain was decreased by 85% after 20 min reperfusion following 20 min ischemia, but was elevated up to 170% after 60 min. [1-13C]glucose increased continuously by up to 370% after 60 min. Total glucose in the fetal liver remained unchanged while [1-13C]glucose increased up to 380%. Total lactate level in brain was 50-80% above the control apart from a transient increase (140%) notable after 40 min reperfusion. The kinetics of [3-13C]lactate followed a similar time course. At the same time when lactate was transiently increased in fetal brain, total lactate as well as 13C-labeled lactate showed a transient decrease in liver after 40 min. While the ways of mobilization of energy substrates for maintaining adequate metabolic activity in the fetal brain remain still unclear, the present 13C NMR studies suggest that both liver glucose and lactate can contribute to brain metabolism particularly under ischemic stress.

Selective increase of brain lactate synthesis in experimental acute liver failure: Results of a [1H-13C] nuclear magnetic resonance study

“…The ratio of [3-13 C]lactate to the concentration of unlabelled lactate (tracer-tracee ratio or "fractional 13 C enrichment") was calculated from 1 H NMR spectra by integration of peak areas of both 1 H- 13 C satellite signals and the 1 H-12 C signal (unlabelled lactate) of the methyl groups ( Fig. 1):…”

“…The values were corrected for 1.1% natural abundance 13 C in unlabelled lactate. 13 C in [1-13 C]glucose was calculated in the same way using the H1␣ glucose resonances in 1 H NMR spectra.…”

“…The values were corrected for 1.1% natural abundance 13 C in unlabelled lactate. 13 C in [1-13 C]glucose was calculated in the same way using the H1␣ glucose resonances in 1 H NMR spectra. The fractional 13 C enrichment of each carbon of other metabolites is derived from peak area ratio of the 13 C-labelled carbon/natural abundance carbon 18 :…”

“…the signal intensity because of natural abundance 13 C in the unlabelled metabolite. The 13 C signal intensities were corrected for NOE (Nuclear Overhauser Enhancement) and naturally abundant 13 C (1.1%) in the 13 C-labelled metabolite.…”

“…The use of nuclear magnetic resonance (NMR) spectroscopy and stable isotope precursors provides an effective approach to the study of metabolic turnover in the brain. In particular, 13 C NMR, which detects 13 C-label in specific carbon positions of individual compounds and allows the simultanous calculation of metabolite concentrations and metabolic fluxes, may be used to track cellular metabolism and intercellular trafficking of substrates in a comprehensive and noninvasive manner. [8][9][10] This technique has been used to determine the relative fluxes via glycolytic and tricarboxylic acid cycle (TCA) pathways as well as to estimate neuronal versus astrocytic metabolism in a "onestep" procedure.…”