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 lacta te (30.8 +/- 3.1 mu mol . kg(-1). min(-1), 2.8 +/- 0.3 mg . kg(-1). mi n(-1)) were remarkably elevated compared with adult values. The interc onversion 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 tricarb oxylic acid cycle. For this purpose, an additional group of six infant s was infused with [3-C-13]lactate, and the distribution of C-13 at sp ecific carbon positions in the glucose molecule was determined using r elevant ions in the electron-impact mass spectrum of its ,2,5,6-diisop ropylidene-3-O-acetyl-alpha-furanosyl derivative; and 3) measuring the reverse conversion of glucose to lactate in five other infants infuse d 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 carbon s 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 an d 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 glucos e turnover, completed the whole glucose-lactate-glucose cycle. In conc lusion, plasma lactate provides four to five times more glucose (per k g body wt) to fasting infants than to adults and is the predominant so urce of endogenous glucose.