Stable isotope determination of plasma lactate conversion into glucose in fasting infants

Abstract

To quantify lactate gluconeogenesis, we developed a gas chromatography-mass spectrometry method based on the infusion of [6,6-2H2]glucose and [3-13C]lactate tracers to 12 infants aged 1-25 mo fasting for 11.5 +/- 1.5 h. Both rates of appearance of plasma glucose (26.7 +/- 2.6 mumol.kg-1.min-1, 4.8 +/- 0.5 mg.kg-1.min-1) and lactate (30.8 +/- 3.1 mumol.kg-1.min-1, 2.8 +/- 0.3 mg.kg-1.min-1) were remarkably elevated compared with adult values. The interconversion of plasma lactate and glucose was determined by 1) measuring the incorporation of 13C from [3-13C]lactate into plasma glucose; 2) correcting for the metabolic exchange of carbon atoms in the tricarboxylic acid cycle. For this purpose, an additional group of six infants was infused with [3-13C]lactate, and the distribution of 13C at specific carbon positions in the glucose molecule was determined using relevant ions in the electron-impact mass spectrum of its 1,2,5,6-diisopropylidene-3-O-acetyl-alpha-furanosyl derivative; and 3) measuring the reverse conversion of glucose to lactate in five other infants infused with [1-13C]glucose. We found that 54 +/- 2% of glucose was derived from plasma lactate (14.4 +/- 1.3 mumol.kg-1.min-1, 2.6 +/- 0.2 mg.kg-1.min-1). Lactate and glucose rates of appearance were correlated (r = 0.58, P < 0.05) and decreased with fasting duration (r = 0.66, P < 0.02). The correction factor for carbon exchange in the tricarboxylic acid cycle was 1.14 +/- 0.11.(ABSTRACT TRUNCATED AT 250 WORDS)