RAPID INTRAVENOUS SODIUM ACETOACETATE INFUSION IN MAN - METABOLIC AND KINETIC RESPONSES
RAPID INTRAVENOUS SODIUM ACETOACETATE INFUSION IN MAN - METABOLIC AND KINETIC RESPONSES
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DOI：
10.1172/jci107453
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发表时间：
1973-01-01
影响因子：
15.9
通讯作者：
SHUMAN, CR
中科院分区：
文献类型：
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作者：
OWEN, OE;REICHARD, GA;SHUMAN, CR
在12名体重为平均体重88 - 215%的男性和女性成年人中，研究了过夜禁食后快速静脉注射乙酰乙酸钠（1.0 mmol/kg体重）的代谢和动力学反应。在输注前、输注期间和输注后采集血液，测定免疫反应性胰岛素、葡萄糖、乙酰乙酸、β-羟基丁酸和游离脂肪酸的循环浓度。在3名肥胖受试者中，在完全饥饿3天和24天后重复研究，过夜后乙酰乙酸快速升高，在输注结束时达到峰值浓度; β-羟基丁酸浓度也迅速升高，并在输注后10分钟超过乙酰乙酸。输注期结束时的总酮体浓度与长时间饥饿后的结果相当。初始混合期后，乙酰乙酸、β-羟基丁酸和总酮体以平行方式迅速下降。受试者之间的酮体血药浓度无明显差异。血浆游离脂肪酸浓度在输注后20 ~ 90 min显著下降;例如0.61毫摩尔/升的对照浓度在60分钟时下降到0.43毫摩尔/升。在重复研究的三个肥胖受试者中，禁食3天后，乙酰乙酸输注使空腹血浆游离脂肪酸从0.92 mmol/L降至0.46 mmol/L，禁食24天后，乙酰乙酸酯输注未引起过夜禁食后血糖浓度的变化。然而，在三个肥胖受试者在禁食3天和24天后重新研究，血糖分别从3.49 mmol/L下降到3.22 mmol/L和从4.07 mmol/L下降到3.49 mmol/L。输注完成时，所有受试者的平均血清胰岛素浓度从21 μU/ml显著升高至46 μU/ml，然后迅速下降。在三个肥胖的受试者重新研究后，3天和24天的禁食一个大约2倍的血清胰岛素增加后，观察到每个乙酰乙酸infration.The平均分数利用率外源性衍生的酮体为所有12名受试者后，过夜的快速是2.9%分钟-1。在研究的3名肥胖受试者中，在过夜、3天和24天禁食后，平均分数利用率分别为2.1%、1.5%和0.6% min-1。整夜禁食受试者的酮体分布体积约为体重的18%-31%，表明酮体在体内水分中分布不均匀。在三个肥胖受试者重新研究后，3天和24天的禁食体积的分布保持大致不变。当血液中的总酮体浓度低于2.0 mmol/L时，酮体利用率与酮体浓度之间存在线性关系;当血液浓度较高时，未发现相关性。图片
The metabolic and kinetic responses to rapidly intravenously administered sodium acetoacetate (1.0 mmol/kg body wt) was studied after an overnight fast in 12 male and female adults weighing between 88 and 215% of average body weight. Blood was obtained before, during, and after the infusion for determination of circulating concentrations of immunoreactive insulin, glucose, acetoacetate, β-hydroxybutyrate and free fatty acids. In three obese subjects the studies were repeated after 3 and 24 days of total starvation.After the overnight fast acetoacetate rose rapidly reaching a peak concentration at the end of the infusion; β-hydroxybutyrate concentrations also increased rapidly and exceeded those of acetoacetate 10 min postinfusion. Total ketone body concentration at the end of the infusion period was comparable to that found after prolonged starvation. After the initial mixing period, acetoacetate, β-hydroxybutyrate and total ketone bodies rapidly declined in a parallel manner. There were no obvious differences between the subjects with regard to their blood concentrations of ketone bodies. The mean plasma free fatty acid concentration decreased significantly during the 20th to 90th min postinfusion period; for example the control concentration of 0.61 mmol/liter fell to 0.43 mmol/liter at 60 min. In the three obese subjects studied repeatedly, fasting plasma free fatty acids decreased with acetoacetate infusion from 0.92 to 0.46 mmol/liter after the 3 day fast and from 1.49 to 0.71 mmol/liter after the 24 day fast. Acetoacetate infusion caused no changes in blood glucose concentration after an overnight fast. However, in the three obese subjects restudied after 3- and 24-day fasts blood glucose decreased, respectively, from 3.49 to 3.22 mmol/liter and from 4.07 to 3.49 mmol/liter. The mean serum insulin concentration in all subjects significantly increased from 21 to 46 μU/ml at the completion of the infusion and rapidly declined. In the three obese subjects restudied after 3- and 24-day fasts an approximate two-fold increase of serum insulin was observed after each acetoacetate infusion.The mean fractional utilization rate of exogenously derived ketone bodies for all 12 subjects after an overnight fast was 2.9% min-1. In the three obese subjects studied after an overnight, 3 and 24 day fast the mean fractional utilization rates were 2.1%, 1.5%, and 0.6% min-1, respectively. Ketone body volumes of distribution in the overnight fasted subjected varied from about 18% to 31% of body wt, suggesting that ketone bodies are not homogenously distributed in the body water. In the three obese subjects restudied after 3- and 24-day fasts volumes of distribution remained approximately constant. When total ketone body concentrations in the blood were below 2.0 mmol/liter, there was a linear relationship between ketone body utilization rates and ketone body concentrations; no correlation was found when blood concentrations were higher.Images