Acute inhibition of lipolysis does not affect postprandial suppression of endogenous glucose production
Acute inhibition of lipolysis does not affect postprandial suppression of endogenous glucose production
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DOI：
10.1152/ajpendo.00195.2005
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发表时间：
2005-12-01
影响因子：
5.1
通讯作者：
Taylor, R
中科院分区：
文献类型：
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作者：
Carey, PE;Gerrard, J;Taylor, R
为了检验肝内脂肪酸利用率可以改变内源性葡萄糖生成（EGP）抑制率的假设，在试验餐前和试验餐期间给予阿昔莫司或安慰剂。我们使用了一种改进的同位素方法来测量EGP在11名健康受试者，和H-1磁共振光谱测量肝脏甘油三酯储存也进行了。阿昔莫司在餐前（0.05 +/- 0.01 mmol/l，-10 min，P = 0）和整个餐后期间（0.03 +/- 0.01 mmol/l，150 min）显著抑制血浆游离脂肪酸。在阿昔莫司治疗日，餐后平均峰值血糖显著降低（8.9 +/- 0.4 vs. 10.1 +/- 0.5 mmol/l，P = 0.01），平均峰值血清胰岛素也是如此（653.1 +/- 99.9 vs. 909 +/- 118 pmol/l，P < 0.01）。空腹EGP相似（11.15 +/- 0.58 mu mol.kg（-1）。min（-1）安慰剂vs. 11.17 +/- 0.89 mg.kg（-1）.min（-1）阿昔莫司）。在2个试验日，餐后EGP的抑制率几乎相同（40分钟时为4.36 +/- 1.52 vs. 3.69 +/- 1.21 mu mol.kg（-1）.min（-1））。阿昔莫司诱导的血糖峰值下降与肝脏甘油三酯含量呈显著负相关（r =-0.827，P = 0.002），表明当肝脏脂肪水平较低时，抑制脂解能够影响葡萄糖稳态。急性药理隔离甘油三酯储存中的脂肪酸改善餐后葡萄糖稳态，而不影响EGP的立即餐后抑制。
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 H-1 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 mu mol.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 mu mol.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.