Measurement of lactate formation from glucose using [6-3H]- and [6-14C]glucose in humans

To assess the validity of determining the origin of plasma lactate from the ratio of lactate and glucose specific activities (SA) during infusion of labeled glucose, normal subjects received infusions of [6-3H]- and [6-14C]glucose for 4 h after a 12 h fast, and, on another day, cold glucose labeled with both tracers during 4-6 h of hyperinsulinemia (approximately 650 microU/ml). Basally, less lactate was derived from plasma glucose when measured with [6-3H]glucose (27 +/- 2%) than with [6-14C]glucose (40 +/- 2%, P less than 0.001). Insulin did not increase the percent of lactate derived from plasma glucose when measured with [6-3H]glucose (29 +/- 2%) but did increase when measured with [6-14C]glucose (60 +/- 4%). The arterialized blood (A) [3H]lactate SA was 30-40% higher (P less than 0.01) than deep venous blood (V) [3H]lactate SA, whereas A and V [14C]lactate SA were similar. During conversion of alanine to lactate with glutamic-pyruvic transaminase (GPT) and lactate dehydrogenase (LDH) in vitro, 32 +/- 2% of 3H in [3-3H]alanine was found in water and 68 +/- 2% in lactate. During infusion of [6-3H]- and [6-14C]glucose, the ratio of [14C]alanine to lactate SA (0.88 +/- 0.05) was less than the ratio of [3H]alanine to lactate SA (0.31 +/- 0.03, P less than 0.001). In conclusion 1) loss of 3H relative to 14C from position 6 in glucose occurs during lactate formation in extrahepatic tissues possibly due to the GPT reaction (alanine conversion to pyruvate), and 2) even under supraphysiologic hyperinsulinemic conditions not all of plasma lactate originates from plasma glucose.