Ferrannini E, Natali A, Brandi L S, Bonadonna R, De Kreutzemberg S V, DelPrato S, Santoro D
Metabolism Unit, University of Pisa, Italy.
Am J Physiol. 1993 Sep;265(3 Pt 1):E504-12. doi: 10.1152/ajpendo.1993.265.3.E504.
Lactate has been suggested to interfere with intermediary metabolism by restricting both lipolysis and glucose utilization. To test this hypothesis, in paired studies in healthy volunteers, sodium lactate (25 mumol.min-1 x kg-1) or saline was infused for 1 h in the fasting state and during 2 h of euglycemic (4.75 mM) hyperinsulinemia (approximately 400 pmol/l). Hyperlactatemia (approximately 2 mM) had no inhibitory effect on fasting free fatty acid or glycerol levels nor did it alter the suppressive action of insulin on these substrates. Likewise, sodium lactate infusion did not influence hepatic glucose production ([3-3H]glucose technique) or its suppression by insulin. During the clamp, hyperlactatemia was associated with a small increase in whole body glucose disposal (34.9 +/- 4.1 vs. 30.3 +/- 3.7 mumol.min-1 x kg-1, P < 0.05) with no major change in the pattern of substrate (carbohydrate vs. lipid) oxidation. By simultaneously measuring arteriovenous gradients across the deep tissues of the forearm (forearm technique), it was found that hyperlactatemia did not impede insulin-mediated glucose uptake; furthermore, it could be estimated that muscle tissues were responsible for the disposal of roughly one-fifth of the lactate load. Whole body energy expenditure was stimulated above the level achieved with hyperinsulinemia when lactate was also infused. Thus, under the present experimental conditions, physiological hyperlactatemia did not interfere with lipolysis, hepatic glucose production, or whole body or forearm muscle glucose utilization, or with insulin action on these processes, and was accompanied by a strong thermogenic effect.
有人提出，乳酸可通过限制脂肪分解和葡萄糖利用来干扰中间代谢。为了验证这一假设，在对健康志愿者进行的配对研究中，在禁食状态下以及在正常血糖（4.75 mM）高胰岛素血症（约400 pmol/l）的2小时期间，输注乳酸钠（25 μmol·min⁻¹·kg⁻¹）或生理盐水1小时。高乳酸血症（约2 mM）对空腹游离脂肪酸或甘油水平没有抑制作用，也没有改变胰岛素对这些底物的抑制作用。同样，输注乳酸钠也不影响肝脏葡萄糖生成（[3-³H]葡萄糖技术）或胰岛素对其的抑制作用。在钳夹期间，高乳酸血症与全身葡萄糖处置的小幅增加有关（34.9±4.1对30.3±3.7 μmol·min⁻¹·kg⁻¹，P<0.05），底物（碳水化合物与脂质）氧化模式没有重大变化。通过同时测量前臂深部组织的动静脉梯度（前臂技术），发现高乳酸血症并不妨碍胰岛素介导的葡萄糖摄取；此外，可以估计肌肉组织负责处理大约五分之一的乳酸负荷。当也输注乳酸时，全身能量消耗比高胰岛素血症时达到的水平更高。因此，在目前的实验条件下，生理性高乳酸血症不干扰脂肪分解、肝脏葡萄糖生成、全身或前臂肌肉葡萄糖利用，或胰岛素对这些过程的作用，并且伴有强烈的产热效应。
