Contribution of liver and skeletal muscle to alanine and lactate metabolism in humans

Abstract

To quantitate alanine and lactate gluconeogenesis in postabsorptive humans and to test the hypothesis that muscle is the principal source of these precursors, we infused normal volunteers with [3-14C]lactate, [3-13C]alanine, and [6-3H]glucose and calculated alanine and lactate incorporation into plasma glucose corrected for tricarboxylic acid cycle carbon exchange, the systemic appearance of these substrates, and their forearm fractional extraction, uptake, and release. Forearm alanine and lactate fractional extraction averaged 37 +/- 3 and 27 +/- 2%, respectively; muscle alanine release (2.94 +/- 0.27 mumol.kg body wt-1.min-1) accounted for approximately 70% of its systemic appearance (4.18 +/- 0.31 mumol.kg body wt-1.min-1); muscle lactate release (5.51 +/- 0.42 mumol.kg body wt-1.min-1) accounted for approximately 40% of its systemic appearance (12.66 +/- 0.77 mumol.kg body wt-1.min-1); muscle alanine and lactate uptake (1.60 +/- 0.7 and 3.29 +/- 0.36 mumol.kg body wt-1.min-1, respectively) accounted for approximately 30% of their overall disappearance from plasma, whereas alanine and lactate incorporation into plasma glucose (1.83 +/- 0.20 and 4.24 +/- 0.44 mumol.kg body wt-1.min-1, respectively) accounted for approximately 50% of their disappearance from plasma. We therefore conclude that muscle is the major source of plasma alanine and lactate in postabsorptive humans and that factors regulating their release from muscle may thus exert an important influence on hepatic gluconeogenesis.

Similar carbohydrate but enhanced lactate utilization during exercise after 9 wk of acclimatization to 5,620 m

“…Thus ϳ45% of the systemic lactate R a originates in skeletal muscle. The contribution of skeletal muscle to systemic lactate R a is similar to the 41% previously reported when forearm lactate release was extrapolated to systemic lactate R a (11). With exercise, the contribution of lactate release from the active legs to the corrected lactate R a is ϳ65% at sea level.…”

Renal glucose production and utilization: new aspects in humans

“…Similar considerations are true for the contribution of the kidney to removal of glucose from the circulation as determined isotopically. Therefore, a combination of net balance and isotopic techniques with measurement of substrate as well as tracer concentrations is necessary to assess individually the uptake and release of a substrate by an organ [29][30][31].…”

Intracellular lactate- and pyruvate-interconversion rates are increased in muscle tissue of non-insulin-dependent diabetic individuals.

“…To exclude blood flow to the hand, a pediatric sphygmomanometric cuff was inflated about the wrist to 100 mmHg above the systolic blood pressure for 3 min before and during each sampling interval. A third 18-gauge intravenous catheter was inserted into a contralateral superficial forearm vein for the initiation of a primed (1.6 g) continuous (1.8 mg/min) infusion of [3][4][5][6][7][8][9][10][11][12][13] C 1 ]-lactate that was kept constant for the ensuing 180 min. After a 2 h isotope equilibration, blood samples were taken simultaneously from the brachial artery and the deep antecubital vein at 15-min intervals over the last hour of the stable isotope infusion for determination of plasma hormone and substrate concentrations as well as 13 C-lactate and 13 C-pyruvate isotope ratios.…”

“…Moreover, much criticism has been raised concerning interpretation of results obtained in studies using lactate tracers. Although arterio-venous balance of labeled lactate was used to assess the possible role of muscle as a lactate source for hepatic gluconeogenesis (3,10), these data have been criticized on the ground that with the tracer method both lactate release and exchange of labeled lactate takes place with intracellular pyruvate. Therefore, the operativity of a lactate-pyruvate exchange would prevent equating uptake of the label with production and utilization of the compound (11)(12)(13), whereas lactate release is only reflected by the rate of conversion of pyruvate to lactate that exceeds that of lactate to pyruvate (14).…”