Department of Medicine and Department of Physiology, Division of Endocrinology and Metabolism, Banting and Best Diabetes Centre, University of Toronto, Toronto, Canada.
Diabetes Obes Metab. 2019 Nov;21(11):2535-2541. doi: 10.1111/dom.13839. Epub 2019 Aug 19.
To test the hypothesis that gut hormone glucagon-like peptide-2 (GLP-2) mobilizes intestinal triglyceride (TG) stores and stimulates chylomicron secretion by a nitric oxide (NO)-dependent mechanism in humans.
In a randomized, single-blind, cross-over study, 10 healthy male volunteers ingested a high-fat formula followed, 7 hours later, by one of three treatments: NO synthase inhibitor L-N -monomethyl arginine acetate (L-NMMA) + GLP-2 analogue teduglutide, normal saline + teduglutide, or L-NMMA + placebo. TG in plasma and lipoprotein fractions were measured, along with measurement of blood flow in superior mesenteric and coeliac arteries using Doppler ultrasound in six participants.
Teduglutide rapidly increased mesenteric blood flow and TG concentrations in plasma, in TG-rich lipoproteins, and most robustly in chylomicrons. L-NMMA significantly attenuated teduglutide-induced enhancement of mesenteric blood flow but not TG mobilization and chylomicron secretion.
GLP-2 mobilization of TG stores and stimulation of chylomicron secretion from the small intestine appears to be independent of systemic NO in humans.
通过实验来验证假说，即肠激素胰高血糖素样肽-2（GLP-2）通过一氧化氮（NO）依赖机制动员肠道甘油三酯（TG）储存并刺激乳糜微粒分泌。
在一项随机、单盲、交叉研究中，10 名健康男性志愿者摄入高脂肪配方，7 小时后接受三种治疗之一：一氧化氮合酶抑制剂 L-N-单甲基精氨酸乙酸盐（L-NMMA）+GLP-2 类似物特利格鲁肽、生理盐水+特利格鲁肽或 L-NMMA+安慰剂。在 6 名参与者中使用多普勒超声测量血浆和脂蛋白中 TG 浓度，同时测量肠系膜上和腹腔动脉血流。
特利格鲁肽迅速增加了肠系膜血流和血浆中 TG 浓度，在富含 TG 的脂蛋白中，尤其是乳糜微粒中。L-NMMA 显著减弱了特利格鲁肽诱导的肠系膜血流增强，但对 TG 动员和乳糜微粒分泌没有影响。
GLP-2 动员 TG 储存并刺激小肠乳糜微粒分泌似乎与人类的系统性 NO 无关。
