游离脂肪酸增高对肝糖产生、葡萄糖循环和总葡萄糖输出率的影响

Effect of free fatty acids on hepatic glucose production, glucose cycling and total glucose output

目的探讨FFA增加肝脏葡萄糖生成和肝脏胰岛素抵抗(IR)的作用位点。方法分别给清醒大鼠输注24h脂肪乳+肝素和盐水,在输注的最后2h行高胰岛素正葡萄糖钳夹试验,测定肝脏葡萄糖生成率(HGP)、总葡萄糖输出率(TGO)和葡萄糖循环(GC)。结果脂肪乳使血浆FFA升高3倍。在基础状态,脂肪乳使HGP和TGO增高(P<0.01)。在钳夹状态,脂肪乳降低了胰岛素(Ins)增加GC的作用(P<0.01),并使Ins抑制HGP和TGO的作用下降(P<0.01)。结论 FFA能使Ins增加GC和抑制HGP与TGO的作用下降,说明FFA在不同位点诱导了肝脏IR。

Objective To investigate the action sites of the free fatty acid （FFA） for increasing hepatic glucose production and hepatic insulin resistance. Methods Intralipid plus heparin （IH group） and saline （SAL group） were infused for 24 hours in Wistar rats. During the last 2 hours of infusion, hepatic glucose production （HGP）, total glucose output （TGO）, glucose cycling（GC） were measured in rats at states of overnight fasting by hyperinsulinemic euglycemic damp. Results FFA levels in IH group were elevated to 3 time the basal level. In the basal state, IH increased TGO （P〈0.01） and HGP （P〈0. 01）. During the clamps, IH decreased the ability of insulin to increase GC and to suppress HGP and TGO （P〈0.01）. Conclusions FFA increases HGP through an increase of TGO and a decrease of GC, which suggests that FFA induces hepatic insulin resistance at different sites.