Owen O E, Reichard G A, Markus H, Boden G, Mozzoli M A, Shuman C R
J Clin Invest. 1973 Oct;52(10):2606-16. doi: 10.1172/JCI107453.
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, beta-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; beta-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, beta-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 muU/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.
对12名体重在平均体重的88%至215%之间的成年男女进行了一项研究，他们在禁食一夜后，快速静脉注射乙酰乙酸钠（1.0 mmol/kg体重），观察其代谢和动力学反应。在输注前、输注期间和输注后采集血液，以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。在三名肥胖受试者中，在完全饥饿3天和24天后重复进行了研究。禁食一夜后，乙酰乙酸迅速上升，在输注结束时达到峰值浓度；β-羟基丁酸浓度也迅速增加，并在输注后10分钟超过乙酰乙酸浓度。输注期结束时总酮体浓度与长期饥饿后发现的浓度相当。在初始混合期之后，乙酰乙酸、β-羟基丁酸和总酮体以平行方式迅速下降。受试者之间酮体的血液浓度没有明显差异。输注后第20至90分钟期间，平均血浆游离脂肪酸浓度显著下降；例如，对照浓度0.61 mmol/升在60分钟时降至0.43 mmol/升。在三名重复研究的肥胖受试者中，禁食血浆游离脂肪酸在输注乙酰乙酸后，禁食3天后从0.92 mmol/升降至0.46 mmol/升，禁食24天后从1.49 mmol/升降至0.71 mmol/升。禁食一夜后，输注乙酰乙酸不会引起血糖浓度变化。然而，在禁食3天和24天后重新研究的三名肥胖受试者中，血糖分别从3.49 mmol/升降至3.22 mmol/升和从4.07 mmol/升降至3.49 mmol/升。所有受试者的平均血清胰岛素浓度在输注结束时从21 μU/ml显著增加到46 μU/ml，并迅速下降。在禁食3天和24天后重新研究的三名肥胖受试者中，每次输注乙酰乙酸后血清胰岛素观察到约两倍的增加。所有12名受试者在禁食一夜后，外源性酮体的平均分数利用率为2.9% min⁻¹。在禁食一夜、3天和24天后研究的三名肥胖受试者中，平均分数利用率分别为2.1%、1.5%和0.6% min⁻¹。禁食一夜的受试者中酮体的分布体积在体重约18%至31%之间变化，表明酮体在体内水中分布不均匀。在禁食3天和24天后重新研究的三名肥胖受试者中，分布体积保持大致恒定。当血液中总酮体浓度低于2.0 mmol/升时，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。
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