Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion
Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion
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DOI：
10.1210/en.140.4.1687
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发表时间：
1999-04-01
期刊：
影响因子：
4.8
通讯作者：
Brubaker, PL
中科院分区：
文献类型：
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作者：
Rocca, AS;Brubaker, PL
胰高血糖素样肽-1（GLP-1）的血浆水平在营养摄入后迅速升高，表明存在近端肠道信号调节远端小肠L细胞的GLP-1释放。葡萄糖依赖性促胰岛素肽（GIP）已被证明是一个这样的近端信号;然而，GIP对胃泌素释放肽（一种神经调节剂）的依赖性表明神经系统在近端-远端环路中的作用。因此，在大鼠胃肠道系统的原位模型中对该近端信号的性质进行了研究。将玉米油注入通过松散结扎分离的10 cm十二指肠段（以确保管腔内容物不会进展到回肠L细胞），增加GLP-1的分泌，与肠道胰高血糖素样免疫反应性平行（gGLI; r = 0.85; P < 0.05）。与盐水灌注相比，将脂肪灌注到横断的十二指肠段中也显著增加了gGLI分泌，达到高于基础值的132 +/- 37 pg/ml的峰值（P < 0.05）。然而，与仅结扎后相比，当肠被横切时，峰值分泌显著延迟（分别为19 +/- 4对6 +/- 1分钟; P < 0.05）。此外，双侧迷走神经下切断联合肠横断完全消除了脂肪诱导的gGLI分泌增加（P < 0.001）。与迷走神经在调节L细胞中的作用一致，刺激小脑下迷走神经的腹腔分支的远端显著刺激gGLI分泌至高于基础水平71 +/-14 pg/ml（P < 0.05）。如前所述，超生理输注GIP使对照动物的gGLI分泌显著增加123 +/- 32 pg/ml（P < 0.05）;肝分支迷走神经切断术不能阻止这一点（96 +/- 25 pg/ml; P < 0.05）。相反，虽然生理水平的GIP输注到假迷走神经切断的动物中也使gGLI分泌增加40 +/- 6 pg/ml（P < 0.05），但选择性肝分支迷走神经切断术消除了GIP诱导的gGLI分泌（P < 0.05）。因此，这些实验的结果表明，响应于脂肪，来自回肠L细胞的GLP-1和gGLI的分泌受复杂的神经内分泌环路调节，涉及肠神经系统、传入和传出迷走神经以及十二指肠激素GIP。
Plasma levels of glucagon-like peptide-1 (GLP-1) rise rapidly after nutrient ingestion, suggesting the existence of a proximal gut signal regulating GLP-1 release from the L cells of the distal small intestine. Glucose-dependent insulinotropic peptide (GIP) has been shown to be one such proximal signal; however, the dependence of GIP on gastrin-releasing peptide, a neuromodulator, suggested a role for the nervous system in this proximal-distal loop. Investigations into the nature of this proximal signal were therefore conducted in an in situ model of the rat gastrointestinal system. Infusions of corn oil into a 10-cm segment of duodenum that was isolated by loose ligation (to ensure that the luminal contents did not progress to the ileal L cell) increased the secretion of GLP-1 in parallel with that of gut glucagon-like immunoreactivity (gGLI; r = 0.85; P < 0.05). Infusion of fat into a transected segment of duodenum also significantly raised gGLI secretion compared with saline infusion, reaching a peak value of 132 +/- 37 pg/ml above basal (P < 0.05). However, peak secretion was significantly delayed when the gut was transected compared with that after ligation alone (19 +/- 4 vs. 6 +/- 1 min, respectively; P < 0.05). Furthermore, bilateral subdiaphragmatic vagotomy in conjunction with gut transection completely abolished the fat-induced rise in gGLI secretion (P < 0.001). Consistent with a role for the vagus in the regulation of the L cell, stimulation of the distal end of the celiac branch of the subdiaphragmatic vagus nerve significantly stimulated the secretion of gGLI to a level of 71 +/- 14 pg/ml above basal (P < 0.05). As found previously, supraphysiological infusion of GIP significantly increased gGLI secretion in control animals by 123 +/- 32 pg/ml (P < 0.05); this was not prevented by hepatic branch vagotomy (96 +/- 25 pg/ml; P < 0.05). In contrast, although infusion of GIP at physiological levels into sham-vagotomized animals also increased gGLI secretion, by 40 +/- 6 pg/ml (P < 0.05), selective hepatic branch vagotomy abolished GIP-induced gGLI secretion (P < 0.05). The results of these experiments therefore demonstrate that the secretion of GLP-1 and gGLI from the ileal L cell in response to fat is regulated by a complex neuroendocrine loop, involving the enteric nervous system, the afferent and efferent vagus nerves, as well as the duodenal hormone GIP.