Exogenous glucagon-like peptide-1 acts in sites supplied by the cranial mesenteric artery to reduce meal size and prolong the intermeal interval in rats.
Exogenous glucagon-like peptide-1 acts in sites supplied by the cranial mesenteric artery to reduce meal size and prolong the intermeal interval in rats.
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DOI：
10.1016/j.appet.2015.09.030
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发表时间：
2016-01-01
期刊：
影响因子：
5.4
通讯作者：
Sayegh AI
中科院分区：
文献类型：
--
作者：
Williams KE;Washington MC;Johnson-Rouse T;Johnson RE;Freeman C;Reed C;Heath J;Sayegh AI
为了更好地评价GLP-1对大鼠摄食量的影响，进行了三个实验，以更好地评价GLP-1在胃肠道(GI)部位(S)的作用。首先，将生理盐水、0.025或0.5nmol/kgGLP-1分别注入大鼠的腹主动脉(CA)、肠系膜动脉(CMA)、股动脉(FA)和门静脉(PV)，测量大鼠夜间近自发的进食大小(MS)、进食间隔(IMI)和饱腹率(SR=MS/IMI)。其次，用GLP-1受体(GLP-1R)拮抗剂exendin-4(3-39)对GLP-1受体拮抗剂(3-39)进行预处理后，按0.5nmol/kg的剂量注入GLP-1。第三，用逆转录聚合酶链式反应检测GLP-1R在大鼠胃肠道的区域分布。CA、CMA和FA GLP-1较生理盐水降低First MS，CMA途径较其他途径更有效。仅CMA-GLP-1延长IMI。没有一种输液影响第二次多发性硬化症或后来的进食。CA和CMA GLP-1增加了SR，且CMA路径比CA路径更有效。CMA exendin-4(3-39)输注可降低CMA-GLP-1的作用。GLP-1R在整个胃肠道均有表达。结果表明，在我们的条件下，外源性GLP-1在多个GI部位起作用，减少摄食，而CMA供应的区域，即大肠和部分小肠的GLP-1R起主导作用。
Three experiments were done to better assess the gastrointestinal (GI) site(s) of action of GLP-1 on food intake in rats. First, near-spontaneous nocturnal chow meal size (MS), intermeal intervals (IMI) length and satiety ratios (SR = MS/IMI) were measured after infusion of saline, 0.025 or 0.5 nmol/kg GLP-1 into the celiac artery (CA, supplying the stomach and upper duodenum), cranial mesenteric artery (CMA, supplying small and all of the large intestine except the rectum), femoral artery (FA, control) or portal vein (PV, control). Second, infusion of 0.5 nmol/kg GLP-1 was tested after pretreatment with the GLP-1 receptor (GLP-1R) antagonist exendin-4(3–39) via the same routes. Third, the regional distribution of GLP-1R in the rat GI tract was determined using rtPCR. CA, CMA and FA GLP-1 reduced first MS relative to saline, with the CMA route more effective than the others. Only CMA GLP-1 prolonged the IMI. None of the infusions affected second MS or later eating. CA and CMA GLP-1 increased the SR, with the CMA route more effective than the CA route. CMA exendin-4 (3–39) infusion reduced the effect of CMA GLP-1. Finally GLP-1R expression was found throughout the GI tract. The results suggest that exogenous GLP-1 acts in multiple GI sites to reduce feeding under our conditions and that GLP-1R in the area supplied by the CMA, i.e., the small and part of the large intestine, plays the leading role.