METABOLISM OF H-3-LABELED AND C-14-LABELED LACTATE IN STARVED RATS

METABOLISM OF H-3-LABELED AND C-14-LABELED LACTATE IN STARVED RATS
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DOI:
10.1042/bj1940525
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发表时间:
1981-01-01
影响因子:
4.1
通讯作者:
KATZ, J
KATZ, J
中科院分区:
生物学3区
文献类型:
--
作者:
OKAJIMA, F;CHENOWETH, M;KATZ, J

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[2-3H通过输注或推注给予过夜饥饿大鼠[3- 3 H,U-14 C]-或[3- 3 H,U-14 C]-乳酸盐。通过留置套管将示踪剂乳酸注射或输注到主动脉中,并从腔静脉中采集血液(A-VC模式),或将其注入腔静脉并从主动脉中采集血液(V-A模式)。输注终止后继续采样,以获得示踪剂的洗脱曲线。测定了乳酸、葡萄糖、氨基酸和水分的活力。标记乳酸在2种模式下的动力学明显不同,但标记葡萄糖的动力学几乎相同,与模式无关。3 H-标记的乳酸的动力学显着不同的[U-14 C]乳酸。[~ 3 H]乳酸盐输注1小时内达到同位素稳态,但[U-14 C]乳酸盐需要6小时以上。来自[2- 3 H]乳酸的3 H比来自[3- 3 H]乳酸的3 H标记葡萄糖更广泛。[3- 3 H]乳酸盐也标记血浆氨基酸。测定了~ 3 H在葡萄糖中的分布。血浆中3 HOH的最大放射性在注射后< 1分钟内达到。注射后2-3 min内,[14 C]葡萄糖和[3 H]葡萄糖的放射性接近最大值。根据预充输注后比放射性曲线下面积或平台比放射性计算乳酸盐的表观置换率。推注和输注计算的结果非常一致。A-VC模式下[3 H]乳酸的表观替代率平均约为16 mg/min/kg体重,V-A模式下约为8.5 mg/min/kg体重。对于A-VC模式,[14 C]乳酸盐的表观速率(不可逆处置速率)为8 mg/min/kg体重,对于V-A模式,为5.5 mg/min/kg体重。根据A-VC模式,乳酸C的表观再循环为55-60%,根据V-A模式为35%。在同位素稳态下,[U-14 C]葡萄糖的比放射性在A-VC和V-A模式下分别为[U-14 C]乳酸的55%和45%。校正14 C在通过草酰乙酸的异源生成中的稀释,超过70%的新合成的葡萄糖被计算为来自循环乳酸。评价乳酸盐和葡萄糖之间的3 H再循环。其对替代率的计算无显著影响,但显著影响[2- 3 H]-和[3- 3 H]-乳酸盐的洗脱曲线下面积,以及体内平均通过时间和总乳酸盐质量的计算。校正再循环,在A-VC模式中,平均通过时间约为3分钟,乳酸盐质量约为50 mg/kg体重,乳酸盐空间约为身体空间的65%。V-A模式产生的质量和乳酸空间约为A-VC模式的1/2。[14 C]乳酸的洗脱曲线下面积是[3 H]乳酸的20-30倍,表观C质量为400-500 mg/kg体重,推测包括葡萄糖、丙酮酸和氨基酸的C,这些C与乳酸的C迅速交换。
[2-3H,U-14C]- or [3-3H,U-14C]-Lactate was administered by infusion or bolus injection to overnight-starved rats. Tracer lactate was injected or infused through indwelling cannulas into the aorta, and blood was sampled from the vena cava (A-VC mode), or it was administered into the vena cava and sampled from the aorta (V-A mode). Sampling was continued after infusion was terminated to obtain the wash-out curves for the tracer. The activities of lactate, glucose, amino acids and water were followed. The kinetics of labeled lactate in the 2 modes differed markedly, but the kinetics of labeled glucose were much the same irrespective of mode. The kinetics of 3H-labeled lactate differed markedly from those for [U-14C]lactate. Isotopic steady state was attained in < 1 h of infusion of [3H]lactate but required over 6 h for [U-14C]lactate. 3H from [2-3H]lactate labels glucose more extensive than does that from [3-3H]lactate. [3-3H]Lactate also labels plasma amino acids. The distribution of 3H in glucose was determined. Maximal radioactivity in 3HOH in plamsa is attained in < 1 min after injection. Near-maximal radioactivity in [14C]glucose and [3H]glucose is attained within 2-3 min after injection. The apparent replacement rates for lactate were calculated from the areas under the specific-radioactivity curves or plateau specific radioactivities after primed infusion. Results calculated from bolus injection and infusion agreed closely. The apparent replacement rate for [3H]lactate from the A-VC mode averaged about 16 mg/min per kg body wt and that in the V-A mode about 8.5 mg/min per kg body wt. The apparent rates for [14C]lactate (rate of irreversible disposal) were 8 mg/min per kg body wt for the A-VC mode and 5.5 mg/min per kg body wt for the V-A mode. Apparent recycling of lactate C was 55-60% according to the A-VC mode and 35% according to the V-A mode. The specific radioactivities of [U-14C]glucose at isotopic steady state were 55 and 45% of [U-14C]lactate in the A-VC and V-A modes, respectively. Correcting for the dilution of 14C in gluconeogenesis via oxaloacetate, over 70% of newly synthesized glucose was calculated to be derived from circulating lactate. Recycling of 3H between lactate and glucose was evaluated. It has no significant effect on the calculation of the replacement rate, but affects considerably the areas under the wash-out curves for both [2-3H]- and [3-3H]-lactate, and calculation of mean transit time and total lactate mass in the body. Corrected for recycling, in the A-VC mode the mean transit time is about 3 min, the lactate mass about 50 mg/kg body wt and the lactate space about 65% of body space. The V-A mode yields a mass and lactate space about 1/2 those with the A-VC mode. The area under the wash-out curve for [14C]lactate is 20-30 times that for [3H]lactate, and apparent C mass is 400-500 mg/kg body wt and presumably includes the C of glucose, pyruvate and amino acids, which are exchanging rapidly with that of lactate.