Effects of intravenous methyl palmoxirate on the turnover and oxidation of fatty acids in conscious dogs.
Effects of intravenous methyl palmoxirate on the turnover and oxidation of fatty acids in conscious dogs.
复制标题
静脉注射棕榈氧酸甲酯对清醒犬脂肪酸周转和氧化的影响。
DOI：
10.1016/0026-0495(91)90155-p
复制
发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Miles,JM
中科院分区：
文献类型：
--
作者：
Bailey,JW;Jensen,MD;Miles,JM
棕榈氧酸甲酯 (MP) 是一类在体外抑制脂肪酸氧化的降血糖药。本文介绍的研究旨在确定静脉注射 (IV) MP 对示踪剂测定的犬脂肪酸氧化速率和全身脂肪组织脂解作用的影响。使用已引发的连续输注[1-14C]棕榈酸酯对五只杂种狗进行静脉注射MP（40mg/kg）以确定棕榈酸酯动力学。棕榈酸酯浓度和出现率迅速下降（15 分钟时分别从 155 ± 25 降至 47 ± 6 μmol/L 和 2.9 ± 0.5 降至 0.9 ± 0.2 μmol·kg−1·min−1，均 P< .05）。棕榈酸酯氧化也降低，从 1.5 ± 0.4 降至 0.3 ± 0.1 μmol·kg−1·min−1，P< .05。 MP 给药后 90 分钟，氧化清除率下降约 50% (P< .05)。棕榈酸酯的氧化分数也降低了约 40% (P< .05)。 15 分钟时血浆胰岛素从 45 ± 6 增加至 240 ± 93 pmol/L (P< .05)。研究过程中血浆葡萄糖下降约 20% (P< .05)。总之，MP 对狗血浆游离脂肪酸 (FFA) 氧化具有特异性抑制作用，证实了先前在体内模型中的体外观察结果。此外，静脉注射时它具有有效的抗脂解作用，这种作用可能是通过刺激胰岛素分泌介导的。在相对高剂量的 MP 下，全身 FFA 氧化仅部分受到抑制，这一观察结果与之前的研究一致，表明 MP 可能在肝脏中发挥其主要作用，而在肝外组织中的作用可能较弱。
Methyl palmoxirate (MP) is a member of a class of hypoglycemic agents that inhibit fatty acid oxidation in vitro. The studies presented here were undertaken to determine the effects of intravenous (IV) MP on tracer-determined rates of fatty acid oxidation and systemic adipose tissue lipolysis in dogs. MP (40 mg/kg) was administered IV to five mongrel dogs using a primed continuous infusion of [1-14C]palmitate to determine palmitate kinetics. Palmitate concentration and rate of appearance decreased rapidly (from 155 ± 25 to 47 ± 6 μmol/L and 2.9 ± 0.5 to 0.9 ± 0.2 μmol·kg−1·min−1, respectively, at 15 minutes, bothP< .05). Palmitate oxidation also decreased, from 1.5 ± 0.4 to 0.3 ± 0.1 μmol·kg−1·min−1,P< .05. Oxidative clearance decreased by approximately 50% 90 minutes after MP administration (P< .05). Fractional oxidation of palmitate also decreased by approximately 40% (P< .05). Plasma insulin increased from 45 ± 6 to 240 ± 93 pmol/L at 15 minutes (P< .05). Plasma glucose decreased over the course of study by approximately 20% (P< .05). In summary, MP has a specific inhibitory effect on plasma free fatty acid (FFA) oxidation in dogs, confirming previous in vitro observations in an in vivo model. In addition, it has a potent antilipolytic effect when administered IV, an effect likely mediated by stimulation of insulin secretion. The observation that systemic FFA oxidation was only partially suppressed at this relatively high dose of MP is consistent with previous studies suggesting that MP may exert its major effect in the liver, and may be less potent in extrahepatic tissues.