Exenatide, a Glucagon-like Peptide-1 Receptor Agonist, Acutely Inhibits Intestinal Lipoprotein Production in Healthy Humans
Exenatide, a Glucagon-like Peptide-1 Receptor Agonist, Acutely Inhibits Intestinal Lipoprotein Production in Healthy Humans
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艾塞那肽是一种胰高血糖素样肽 1 受体激动剂，可急性抑制健康人肠道脂蛋白的产生
DOI：
10.1161/atvbaha.112.246207
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
G. Lewis
中科院分区：
文献类型：
--
作者：
C. Xiao;R. Bandsma;Satya Dash;L. Szeto;G. Lewis
目的——以肠促胰岛素为基础的治疗 2 型糖尿病的疗法可改善血浆脂质谱和餐后血脂，但其确切作用机制仍不清楚。在这里，我们研究了胰高血糖素样肽 1 受体激动剂艾塞那肽对健康人肠道和肝脏富含甘油三酯的脂蛋白产生和清除的急性影响。方法和结果 — 15 名血脂正常、血糖正常的男性每人接受 2 项研究（SC 10 µg 艾塞那肽与安慰剂），间隔 4 至 6 周，随机顺序，其中用引发的、持续输注的氘化亮氨酸检查富含甘油三酯的脂蛋白颗粒动力学，并在胰腺钳夹条件下通过多室模型进行分析。在每次研究期间，通过鼻十二指肠管将高脂肪、混合常量营养素、液体配方以恒定速率直接注入十二指肠来维持进食状态。艾塞那肽显着抑制富含甘油三酯的脂蛋白-载脂蛋白B-48的血浆浓度和生成率，但不抑制富含甘油三酯的脂蛋白-载脂蛋白B-100的血浆浓度和生成率。结论——这些结果表明艾塞那肽可能对肠道脂蛋白颗粒产生产生直接影响，与长期研究中观察到的体重增加和饱腹感的变化无关，也与胃排空的变化无关。这一发现扩展了我们对艾塞那肽在代谢调节中的作用的理解，超出了其在调节葡萄糖稳态中的主要治疗作用。临床试验注册——URL：http://www.clinicaltrials.gov，NCT01056549。
Objectives—Incretin-based therapies for the treatment of type 2 diabetes mellitus improve plasma lipid profiles and postprandial lipemia, but their exact mechanism of action remains unclear. Here, we examined the acute effect of the glucagon-like peptide-1 receptor agonist, exenatide, on intestinal and hepatic triglyceride-rich lipoprotein production and clearance in healthy humans. Methods and Results—Fifteen normolipidemic, normoglycemic men underwent 2 studies each (SC 10 &mgr;g exenatide versus placebo), 4 to 6 weeks apart, in random order, in which triglyceride-rich lipoprotein particle kinetics were examined with a primed, constant infusion of deuterated leucine and analyzed by multicompartmental modeling under pancreatic clamp conditions. A fed state was maintained during each study by infusing a high-fat, mixed macronutrient, liquid formula at a constant rate directly into the duodenum via a nasoduodenal tube. Exenatide significantly suppressed the plasma concentration and production rate of triglyceride-rich lipoprotein-apolipoprotein B-48, but not of triglyceride-rich lipoprotein-apolipoprotein B-100. Conclusions—These results suggest a possible direct effect of exenatide on intestinal lipoprotein particle production, independent of changes in weight gain and satiety as seen in long-term studies and independent of changes in gastric emptying. This finding expands our understanding of the effects of exenatide in metabolic regulation beyond its primary therapeutic role in regulation of glucose homeostasis. Clinical Trial Registration—URL: http://www.clinicaltrials.gov, NCT01056549.
DOI：
10.1152/ajpendo.90222.2008
发表时间：
2008-08-01
影响因子：
5.1
作者：
Ionut, Viorica;Zheng, Dan;Bergman, Richard N.
通讯作者：
Bergman, Richard N.
影响因子：
4.8
作者：
Ayala, Julio E.;Bracy, Deanna P.;Drucker, Daniel J.
通讯作者：
Drucker, Daniel J.
影响因子：
3.2
作者：
Egan, BM;Greene, EL;Goodfriend, TL
通讯作者：
Goodfriend, TL