Schirra J, Nicolaus M, Woerle H J, Struckmeier C, Katschinski M, Göke B
Department of Internal Medicine II, Ludwig-Maximilians University, Munich, Germany.
Neurogastroenterol Motil. 2009 Jun;21(6):609-18, e21-2. doi: 10.1111/j.1365-2982.2008.01246.x. Epub 2009 Feb 6.
The gut-born incretin hormone glucagon-like peptide-1 (GLP-1) delays gastric emptying. To elucidate the mechanisms by which GLP-1 affects gastroduodenal motility and glycaemia, we studied the effects of exendin(9-39), a potent GLP-1 receptor antagonist, on gastroduodenal motility and pancreatic hormones. In this randomized, double-blind, placebo-controlled, four-arm, cross-over trial, 10 healthy volunteers were studied during the interdigestive period followed by duodenal perfusion of a mixed liquid meal (250 kcal). On four separate days, exendin(9-39), atropine, exendin(9-39) + atropine or saline were infused intravenously. Antro-pyloro-duodenal and fundic motility were assessed. The compliance of the proximal stomach was determined by isobaric distensions. During fasting, exendin(9-39) did not influence proximal gastric volume, pyloric tone, and duodenal contractility. Exendin(9-39) significantly increased antral waves only in the absence of atropine. During duodenal meal perfusion, exendin(9-39) significantly reduced proximal gastric volume accommodation, abbreviated postprandial antral inhibition, reduced the postprandial increase in pyloric tone, and reduced gastric compliance. Atropine abolished the effects of exendin(9-39) on gastric volume accommodation but did not affect its effects on postprandial antroduodenal motility and on gastric compliance. Exendin(9-39) increased fasting and postprandial glycaemia and plasma glucagon but not insulin concentrations. Atropine did not affect GLP-1 secretion. Cholinergic mechanisms mediate the effects of GLP-1 on postprandial gastric accommodation but not on antro-pyloro-duodenal motility. GLP-1 reduces fasting and postprandial glycaemia, in part by reducing glucagon secretion.
肠道源性肠促胰岛素激素胰高血糖素样肽-1（GLP-1）可延缓胃排空。为阐明GLP-1影响胃十二指肠运动和血糖的机制，我们研究了强效GLP-1受体拮抗剂艾塞那肽（9-39）对胃十二指肠运动和胰腺激素的影响。在这项随机、双盲、安慰剂对照、四臂、交叉试验中，对10名健康志愿者在消化间期进行研究，随后十二指肠灌注混合流食（250千卡）。在四个不同的日子里，静脉输注艾塞那肽（9-39）、阿托品、艾塞那肽（9-39）+阿托品或生理盐水。评估胃窦-幽门-十二指肠和胃底的运动。通过等压扩张测定近端胃的顺应性。在禁食期间，艾塞那肽（9-39）不影响近端胃容积、幽门张力和十二指肠收缩性。仅在没有阿托品的情况下，艾塞那肽（9-39）显著增加胃窦波。在十二指肠灌注餐期间，艾塞那肽（9-39）显著减少近端胃容积容纳，缩短餐后胃窦抑制，降低餐后幽门张力增加，并降低胃顺应性。阿托品消除了艾塞那肽（9-39）对胃容积容纳的影响，但不影响其对餐后胃十二指肠运动和胃顺应性的影响。艾塞那肽（9-39）增加禁食和餐后血糖及血浆胰高血糖素浓度，但不影响胰岛素浓度。阿托品不影响GLP-1分泌。胆碱能机制介导GLP-1对餐后胃容纳的影响，但不介导对胃窦-幽门-十二指肠运动的影响。GLP-1降低禁食和餐后血糖，部分是通过减少胰高血糖素分泌实现的。
