STABLE-ISOTOPE DETERMINATION OF PLASMA LACTATE CONVERSION INTO GLUCOSE IN FASTING INFANTS

To quantify lactate gluconeogenesis, we developed a gas chromatography-mass spectrometry method based on the infusion of [6,6-H-2(2)]glucose and [3-C-13]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 mu mol . kg(-1). min(-1), 4.8 +/- 0.5 mg . kg(-1). min(-1)) and lactate (30.8 +/- 3.1 mu mol . 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 C-13 from [3-C-13]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-C-13]lactate, and the distribution of C-13 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-C-13]glucose. We found that 54 +/- 2% of glucose was derived from plasma lactate (14.4 +/- 1.3 mu mol . 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. The flux of glucose carbons converted into lactate was 5.5 +/- 0.04 mu mol . kg(-1). min(-1) (1.0 +/- 0.2 mg . kg(-1). min(-1)), i.e., 21% of glucose disappearance and 25% of lactate appearance in plasma. Only 3.2 +/- 0.2 mu mol glucose . kg(-1). min(-1) (0.6 +/- 0.1 mg . kg(-1). min(-1)), 12.5% of glucose turnover, completed the whole glucose-lactate-glucose cycle. In conclusion, plasma lactate provides four to five times more glucose (per kg body wt) to fasting infants than to adults and is the predominant source of endogenous glucose.