The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjects
The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjects
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DOI：
10.1172/jci5479
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发表时间：
1999-02-01
影响因子：
15.9
通讯作者：
Boden, G
中科院分区：
文献类型：
--
作者：
Chen, XH;Iqbal, N;Boden, G
我们已经定量测定了所有前体的GNG，使用一种新的方法，采用（H2O）-H-2来解决血浆游离脂肪酸（FFA）的变化是否会影响健康，非肥胖受试者的GNG的问题。在第一项研究（n = 6）中，烟酸（NA）在16至20小时降低血浆FFA，然后在20至24小时升高（NA给药后FFA反弹）。FFA从16小时的387 μ M下降到20小时的43 μ M，然后在24小时反弹到1，823 μ M。GNG从16小时的58.1%下降到20小时的38.6%（P < 0.005），然后回升到24小时的78.9%（P < 0.05）。相反，糖原分解（GL）从16小时的41.9%增加到20小时的61.4%（P < 0.05），然后下降到24小时的21.1%（P < 0.05）。在第二项研究中（对照组; n = 6），在最后一餐后16至24小时对志愿者进行了分析。FFA从423 μ M上升到681 μ M（P < 0.05），GNG从50.3%上升到61.7%（P < 0.02），而GL从49.7%下降到38.3%（P < 0.05）。两项研究中内源性葡萄糖产量以相同的速率下降，从10.7 μ mol/kg/min降至8.6 μ mol/kg/min（P < 0.05）。在研究3（n = 6）中，通过输注脂质和肝素防止了NA介导的血浆FFA降低，FFA和GNG均未发生显著变化。总之，我们的数据表明：（a）血浆FFA的急性变化引起GNG的急性变化和GL的相互变化;（B）空腹16至24小时之间EGP的降低是由于GL的下降;（c）NA对GNG没有直接影响。
We have quantitatively determined gluconeogenesis (GNG) from all precursors, using a novel method employing (H2O)-H-2 to address the question of whether changes in plasma free fatty acids (FFA) affect GNG in healthy, nonobese subjects. In the first study (n = 6), plasma FFA were lowered at 16 to 20 hours with nicotinic acid (NA) and were then allowed to rise at 20 to 24 hours (FFA rebound after administration of NA). FFA decreased from 387 mu M at 16 hours to 43 mu M at 20 hours, and then rebounded to 1,823 mu M at 24 hours. GNG decreased from 58.1% at 16 hours to 38.6% of endogenous glucose production at 20 hours (P < 0.005) and then rebounded to 78.9% at 24 hours (P < 0.05). Conversely, glycogenolysis (GL) increased from 41.9% at 16 hours to 61.4% at 20 hours (P < 0.05), and then decreased to 21.1% at 24 hours (P < 0.05). In the second study (controls; n = 6), volunteers were analyzed between 16 and 24 hours after the last meal. FFA rose from 423 to 681 mu M (P < 0.05), and GNG from 50.3% to 61.7% (P < 0.02), whereas GL decreased from 49.7% to 38.3% (P < 0.05). Endogenous glucose production decreased at the same rate in both studies, from 10.7 to 8.6 mu mol/kg/min (P < 0.05). In study 3 (n = 6), in which the NA-mediated decrease of plasma FFA was prevented by infusion of lipid and heparin, neither FFA nor GNG changed significantly. In summary, our data suggest that (a) acute changes in plasma FFA produce acute changes in GNG and reciprocal changes in GL; (b) the decrease in EGP between 16 and 24 hours of fasting is due to a fall in GL; and (c) NA has no direct effect on GNG.