GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets
GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets
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DOI：
10.1016/s0016-5085(03)00667-x
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发表时间：
2003-07-01
期刊：
影响因子：
29.4
通讯作者：
Burrin, DG
中科院分区：
文献类型：
--
作者：
Guan, XF;Stoll, B;Burrin, DG
背景和目标：我们的目的是确定GLP-2的促神经营养作用是否通过TPN喂养仔猪肠道底物利用的急性上调介导。方法：24只12日龄猪，安装门静脉血流探头和颈动脉、颈静脉和门静脉导管，经TPN喂养7天。在第8天，向一组猪（n = 8）静脉内输注盐水（对照）4小时，然后输注GLP-2（500 pmol . kg（-1）。小时（-1），GLP-2）4小时。输注H-2-葡萄糖和C-13-苯丙氨酸以估计其动力学和蛋白质周转。另一组（n = 8）接受连续静脉输注生理盐水、GLP-2和GLP-2加N-G-硝基-L-精氨酸甲酯（L-NAME，50 μ mol. kg（-1）。小时（-1）），每次4小时。结果：GLP-2在TPN喂养的仔猪中急性增加门静脉引流内脏（PDV）血流速率（+25%）和肠血容量（+51%）。GLP-2还增加肠组成型一氧化氮合酶（NOS）活性和内皮NOS蛋白丰度。GLP-2急剧增加PDV葡萄糖摄入（+90%）和净乳酸产生（+79%）。GLP-2加L-NAME的共输注不增加PDV血流速率或葡萄糖摄取。GLP-2使PDV必需氨基酸摄取增加220%，蛋白质合成增加125%，但不降低蛋白质分解或苯丙氨酸氧化。结论：我们的结论是，在TPN喂养的新生猪，GLP-2急性刺激肠血流量和葡萄糖的利用，这种反应是一氧化氮依赖性的。这些发现表明，GLP-2可能在调节肠血流中发挥重要的生理作用，一氧化氮参与GLP-2受体功能。
Background & Aims: Our aim was to determine whether the intestinotrophic effects of GLP-2 are mediated by acute up-regulation of intestinal substrate utilization in TPN-fed piglets. Methods: Twenty-four 12-day-old pigs, fitted with a portal flow probe and carotid, jugular and portal catheters, were fed by TPN for 7 days. On day 8, a group of pigs (n = 8) was infused intravenously with saline (control) for 4 hours and then with GLP-2 (500 pmol . kg(-1) . hour(-1), GLP-2) for 4 hours. H-2-glucose and C-13-phenylalanine were infused to estimate their kinetics and protein turnover. Another group (n = 8) received consecutive intravenous infusions of saline, GLP-2, and GLP-2 plus N-G-Nitro-L-arginine methyl ester (L-NAME, 50 mumol . kg(-1) . hour(-1)) for 4 hours each. Results: GLP-2 acutely increased portal-drained visceral (PDV) blood flow rate (+25%) and intestinal blood volume (+51%) in TPN-fed piglets. GLP-2 also increased intestinal constitutive nitric oxide synthase (NOS) activity and endothelial NOS protein abundance. GLP-2 acutely increased PDV glucose uptake (+90%) and net lactate production (+79%). Co-infusion of GLP-2 plus L-NAME did not increase either PDV blood flow rate or glucose uptake. GLP-2 increased PDV indispensable amino acid uptake by 220% and protein synthesis by 125%, but did not decrease protein breakdown or phenylalanine oxidation. Conclusions: We conclude that in TPN-fed neonatal pigs, GLP-2 acutely stimulates intestinal blood flow and glucose utilization, and this response is nitric oxide-dependent. These findings suggest that GLP-2 may play an important physiological role in the regulation of intestinal blood flow and that nitric oxide is involved in GLP-2 receptor function.