Evidence of hepatic glucagon resistance associated with hepatic steatosis: Reversal effect of training
Evidence of hepatic glucagon resistance associated with hepatic steatosis: Reversal effect of training
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DOI：
10.1055/s-2004-821225
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发表时间：
2005-07-01
影响因子：
2.5
通讯作者：
Lavoie, JM
中科院分区：
文献类型：
--
作者：
Charbonneau, A;Couturier, K;Lavoie, JM
本研究旨在验证以下假设：高脂饮食诱导的肝脂肪变性与高胰高血糖素输注引起的肝葡萄糖输出量（HGO）减少相关，并且高脂饮食大鼠的肝胰高血糖素抵抗的假设状态可通过同步运动训练减弱。在四组麻醉大鼠中，胰高血糖素（2 μ g/kg/min iv）在60分钟内输注，以测量HGO。给两组大鼠喂食标准（SD）或高脂肪（1117; 42%千卡）饮食8周，并将其分配到久坐（Sed）组或健身房训练的JR组。训练在饮食方案开始后两周开始，并在6周的时间内逐渐增加，最后3周以26 m/min，10%等级达到60 min。与SD饮食相比，HF导致Sed大鼠的肝脏甘油三酯水平高出28%（p < 0.01）。HF-TR组的运动训练计划完全阻止了这种增加。除SD-Sed组胰岛素水平较高（p < 0.05）外，所有四组的血浆胰高血糖素（类似于90000 pg/ml）和胰岛素（类似于500 pmol/l）水平均升高至相似程度。SD-Sed中的胰高血糖素（类似于300 mg/dl）高于HF-Sed和SD-TR组（p < 0.05）。与SD-Sed组相比，胰高血糖素输注导致HF-Sed中HGO的显著（p < 0.05）较低的增加（类似于35%）。无论在胰高血糖素输注25、40或60分钟后测量HGO，观察到HF-Sed大鼠的HGO水平低于SD-Sed大鼠。HF喂养大鼠的运动训练导致HF-包括胰高血糖素抵抗状态的显著（p < 0.05）减弱（50%）。所有个体肝脏甘油三酯和60分钟HGO值的比较显示，肝脏甘油三酯值高度（p < 0.001）预测胰高血糖素对HGO作用的降低（R =-0.849）。目前的研究结果表明，喂养高脂肪饮食诱导肝胰高血糖素抵抗的状态，这是部分衰减的同时运动训练。提示肝脏脂质浸润可能干扰胰高血糖素的作用，从而导致肝脏胰高血糖素抵抗。
The present study was undertaken to test the hypothesis that a high-fat diet-induced hepatic steatosis is associated with a reduction in hepatic glucose output (HGO) in response to a hyperglucagonernic infusilon, and that this postulated state of hepatic glucagon resistance in high-fat fed rats is attenuated by concurrent exercise training. In four groups of anesthetized rats, glucagon (2 ug/kg/min iv) was infused over a period of 60 min to measure HGO. Two groups of rats were either fed a standard (SD) or a high-fat (1117; 42% kcal) diet for eight weeks and were assigned either to a Sedentary (Sed) or a treadmill-trained JR) group. Training was initiated two weeks after the beginning of the diet protocol and was progressively increased over a period of 6 weeks reaching 60 min at 26 m/min, 10% grade, for the last 3 weeks. The HF compared to the SD diet resulted in similar to 28 % higher (p < 0.01) liver triglyceride levels in Sed rats. This increase was completely prevented by the exercise training program in the HF-TR group. Plasma glucagon (similar to 90000pg/ml) and insulin (similar to 500 pmol/l) levels were increased to a similar extent in all four groups, with the exception of higher (p < 0.05) insulin levels in SD-Sed group. Glucagon incluced-hyperglycemia (similar to 300mg/dl) was higher (p < 0.05) in the SD-Sed than in HF-Sed and SD-TR groups. Glucagon infusion resulted in a significantly (p < 0.05) lower increase (similar to 35%) in HGO in HF-Sed compared to SD-Sed group. The lower level of HGO in HF-Sed compared to SD-Sed rats was observed whether HGO was measured after 25,40, or 60 min of glucagon infusion. Exercise training in HF fed rats resulted in a significant (p < 0.05) attenuation (50%) of the state of HF-incluced glucagon resistance. Comparisons of all individual liver triglyceride and 60-min HGO values revealed that liver triglyceride values were highly (p < 0.001) predictive of the decreased glucagon action on HGO (R = - 0.849). The present results indicate that the feeding of a high-fat diet induces a state of hepatic glucagon resistance, which is partially attenuated by concurrent exercise training. It is suggested that liver lipid infiltration may interfere with the action of glucagon, thus inducing glucagon resistance in liver.