Anini Younes, Hansotia Tanya, Brubaker Patricia L
Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Endocrinology. 2002 Jun;143(6):2420-6. doi: 10.1210/endo.143.6.8840.
Plasma levels of glucagon-like peptide-1 (GLP-1) rise rapidly after nutrient ingestion through an indirect mechanism triggered from the proximal intestine and involving the vagus nerve that stimulates the L cell in the distal gut. The role of muscarinic receptors in this pathway was thus investigated using the anesthetized rat and fetal rat intestinal cells (FRIC) in culture. GLP-1 secretion from the distal gut increased 5-fold after 3 ml corn oil were placed into the proximal duodenum (P < 0.001). Atropine (a nonspecific muscarinic receptor antagonist) completely inhibited fat-induced GLP-1 secretion in vivo (P < 0.01). Pirenzepine (an M1 muscarinic receptor antagonist) also inhibited fat-induced GLP-1 secretion in vivo, by 91 +/- 6% (P < 0.01). Gallamine (an M2 muscarinic receptor antagonist) and 4-diphenylacetoxy-N-methylpiperidine (an M3 muscarinic receptor antagonist) had no effect. Incubating FRIC cultures with bethanechol (a muscarinic receptor agonist) stimulated GLP-1 secretion to 200 +/- 22% of control (P < 0.01). Pirenzepine and gallamine significantly inhibited bethanechol-stimulated GLP-1 secretion, by 96 +/- 12% and 98 +/- 8%, respectively (P < 0.01). Unexpectedly, 4-diphenylacetoxy-N-methylpiperidine stimulated GLP-1 secretion by FRIC cells, to 324 +/- 52% of the control value (P < 0.01). Double immunofluorescent staining using GLP-1 and M1, M2, and M3 muscarinic receptor antibodies showed expression of the three subtypes of muscarinic receptors by the L cells in rat ileal sections and FRIC cultures. These results demonstrate the role of M1 muscarinic receptors expressed by L cells in the control of postprandial secretion of GLP-1. M2 muscarinic receptors also seem to play a role in controlling GLP-1 secretion by fetal, but not adult, L cells.
营养物质摄入后，血浆中胰高血糖素样肽-1（GLP-1）水平通过近端肠道触发的间接机制迅速升高，该机制涉及迷走神经，刺激远端肠道的L细胞。因此，使用麻醉大鼠和培养的胎鼠肠道细胞（FRIC）研究了毒蕈碱受体在该途径中的作用。将3 ml玉米油注入近端十二指肠后，远端肠道的GLP-1分泌增加了5倍（P < 0.001）。阿托品（一种非特异性毒蕈碱受体拮抗剂）在体内完全抑制了脂肪诱导的GLP-1分泌（P < 0.01）。哌仑西平（一种M1毒蕈碱受体拮抗剂）在体内也抑制了脂肪诱导的GLP-1分泌，抑制率为91±6%（P < 0.01）。加拉明（一种M2毒蕈碱受体拮抗剂）和4-二苯基乙酰氧基-N-甲基哌啶（一种M3毒蕈碱受体拮抗剂）没有作用。用氨甲酰甲胆碱（一种毒蕈碱受体激动剂）孵育FRIC培养物可刺激GLP-1分泌至对照的200±22%（P < 0.01）。哌仑西平和加拉明分别显著抑制氨甲酰甲胆碱刺激的GLP-1分泌，抑制率分别为96±12%和98±8%（P < 0.01）。出乎意料的是，4-二苯基乙酰氧基-N-甲基哌啶刺激FRIC细胞分泌GLP-1，达到对照值的324±52%（P < 0.01）。使用GLP-和M1、M2和M3毒蕈碱受体抗体进行的双重免疫荧光染色显示，大鼠回肠切片和FRIC培养物中的L细胞表达了三种毒蕈碱受体亚型。这些结果证明了L细胞表达的M1毒蕈碱受体在控制餐后GLP-1分泌中的作用。M2毒蕈碱受体似乎也在控制胎儿而非成年L细胞的GLP-1分泌中发挥作用。
