Carey Peter E, Gerrard Jean, Cline Gary W, Dalla Man Chiara, English Philip T, Firbank Michael J, Cobelli Claudio, Taylor Roy
Dept. of Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Am J Physiol Endocrinol Metab. 2005 Dec;289(6):E941-7. doi: 10.1152/ajpendo.00195.2005. Epub 2005 Jul 5.
To test the hypothesis that intrahepatic availability of fatty acid could modify the rate of suppression of endogenous glucose production (EGP), acipimox or placebo was administered before and during a test meal. We used a modified isotopic methodology to measure EGP in 11 healthy subjects, and (1)H magnetic resonance spectroscopic measurement of hepatic triglyceride stores was also undertaken. Acipimox suppressed plasma free fatty acids markedly before the meal (0.05 +/- 0.01 mmol/l at -10 min, P = 0) and throughout the postprandial period (0.03 +/- 0.01 mmol/l at 150 min). Mean peak plasma glucose was significantly lower after the meal on acipimox days (8.9 +/- 0.4 vs. 10.1 +/- 0.5 mmol/l, P < 0.01), as was mean peak serum insulin (653.1 +/- 99.9 vs. 909 +/- 118 pmol/l, P < 0.01). Fasting EGP was similar (11.15 +/- 0.58 micromol.kg(-1).min(-1) placebo vs. 11.17 +/- 0.89 mg.kg(-1).min(-1) acipimox). The rate of suppression of EGP after the meal was almost identical on the 2 test days (4.36 +/- 1.52 vs. 3.69 +/- 1.21 micromol.kg(-1).min(-1) at 40 min). There was a significant negative correlation between the acipimox-induced decrease in peak plasma glucose and liver triglyceride content (r = -0.827, P = 0.002), suggesting that, when levels of liver fat were low, inhibition of lipolysis was able to affect glucose homeostasis. Acute pharmacological sequestration of fatty acids in triglyceride stores improves postprandial glucose homeostasis without effect on the immediate postprandial suppression of EGP.
为了验证肝内脂肪酸可用性可改变内源性葡萄糖生成（EGP）抑制率这一假说，在试餐前后给予阿西莫司或安慰剂。我们采用改良的同位素方法测量了11名健康受试者的EGP，并进行了肝脏甘油三酯储备的氢磁共振波谱测量。阿西莫司在餐前显著抑制血浆游离脂肪酸（-10分钟时为0.05±0.01 mmol/l，P = 0），且在整个餐后期间均有抑制作用（150分钟时为0.03±0.01 mmol/l）。在服用阿西莫司的日子里，餐后平均血糖峰值显著更低（8.9±0.4 vs. 10.1±0.5 mmol/l，P < 0.01），平均血清胰岛素峰值也是如此（653.1±99.9 vs. 909±118 pmol/l，P < 0.01）。空腹EGP相似（安慰剂组为11.15±0.58 μmol·kg⁻¹·min⁻¹，阿西莫司组为11.17±0.89 mg·kg⁻¹·min⁻¹）。在两个测试日，餐后EGP的抑制率几乎相同（40分钟时分别为4.36±1.52 vs. 3.69±1.21 μmol·kg⁻¹·min⁻¹）。阿西莫司诱导的血浆葡萄糖峰值降低与肝脏甘油三酯含量之间存在显著负相关（r = -0.827，P = 0.002），这表明当肝脏脂肪水平较低时，脂解抑制能够影响葡萄糖稳态。甘油三酯储备中脂肪酸的急性药理学隔离可改善餐后葡萄糖稳态，而对餐后即刻EGP的抑制无影响。
