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首页> 外文期刊>American Journal of Physiology >Effects of intraportal exenatide on hepatic glucose metabolism in the conscious dog
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Effects of intraportal exenatide on hepatic glucose metabolism in the conscious dog

机译：门内艾塞那肽对清醒犬肝糖代谢的影响

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Incretins improve glucose metabolism through multiple mechanisms. It remains unclear whether direct hepatic effects are an important part of exenatide's (Ex-4) acute action. Therefore, the objective of this study was to determine the effect of intraportal delivery of Ex-4 on hepatic glucose production and uptake. Fasted conscious dogs were studied during a hyperglycemic clamp in which glucose was infused into the hepatic portal vein. At the same time, portal saline (control; n = 8) or exenatide was infused at low (0.3 pmol·kg-1·min-1, Ex-4-low; n = 5) or high (0.9 pmol·kg-1·min-1, Ex-4-high; n = 8) rates. Arterial plasma glucose levels were maintained at 160 mg/dl during the experimental period. This required a greater rate of glucose infusion in the Ex-4-high group (1.5 ± 0.4, 2.0 ± 0.7, and 3.7 ± 0.7 mg·kg-1·min-1 between 30 and 240 min in the control, Ex-4-low, and Ex-4-high groups, respectively). Plasma insulin levels were elevated by Ex-4 (arterial: 4,745 ± 428, 5,710 ± 355, and 7,262 ± 1,053 μU/ml; hepatic sinusoidal: 14,679 ± 1,700, 15,341 ± 2,208, and 20,445 ± 4,020 μU/ml, 240 min, area under the curve), whereas the suppression of glucagon was nearly maximal in all groups. Although glucose utilization was greater during Ex-4 infusion (5.92 ± 0.53, 6.41 ± 0.57, and 8.12 ± 0.54 mg·kg-1·min-1), when indices of hepatic, muscle, and whole body glucose uptake were expressed relative to circulating insulin concentrations, there was no indication of insulin-independent effects of Ex-4. Thus, this study does not support the notion that Ex-4 generates acute changes in hepatic glucose metabolism through direct effects on the liver.
机译：肠抑素通过多种机制改善葡萄糖代谢。尚不清楚直接肝功能是否是艾塞那肽（Ex-4）急性作用的重要组成部分。因此，本研究的目的是确定门静脉内输送Ex-4对肝葡萄糖生成和摄取的影响。在将血糖注入肝门静脉的高血糖钳位期间研究禁食的清醒狗。同时，以低（0.3 pmol·kg-1·min-1，Ex-4-low; n = 5）或高（0.9 pmol·kg- 1·min-1，Ex-4-high; n = 8）比率。在实验期间，动脉血浆葡萄糖水平维持在160 mg / dl。在Ex-4高组中，这需要更高的葡萄糖输注率（在对照组中，Ex-4在30至240分钟之间为1.5±0.4、2.0±0.7和3.7±0.7 mg·kg-1·min-1 -low组和Ex-4-high组）。血浆胰岛素水平通过Ex-4升高（动脉：4,745±428、5,710±355和7,262±1,053μU/ ml;肝正弦曲线：14,679±1,700、15,341±2,208和20,445±4,020μU/ ml，240分钟，曲线下的面积），而所有组中胰高血糖素的抑制作用几乎都达到最大。尽管在Ex-4输注期间葡萄糖利用率更高（5.92±0.53、6.41±0.57和8.12±0.54 mg·kg-1·min-1），但相对于肝脏，肌肉和全身葡萄糖摄取的指标表示循环胰岛素浓度，没有迹象表明Ex-4具有胰岛素非依赖性作用。因此，本研究不支持Ex-4通过直接作用于肝脏而在肝脏葡萄糖代谢中产生急性变化的观点。

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