Kolligs F, Fehmann H C, Göke R, Göke B
Department of Internal Medicine, Philipps University of Marburg, Germany.
Diabetes. 1995 Jan;44(1):16-9. doi: 10.2337/diab.44.1.16.
Glucagon-like peptide 1 (7-37)/(7-36) amide (GLP-1) is derived from the intestinal proglucagon processing. It is considered an important insulin-releasing gut hormone. This study uses exendin (9-39) amide as a GLP-1 receptor antagonist to evaluate the contribution of GLP-1 to the incretin effect. Anesthetized rats were challenged by an intraduodenal glucose infusion to evaluate maximally occurring GLP-1 and gastric inhibitory polypeptide (GIP) plasma levels. Maximal immunoreactive (IR) GLP-1 plasma levels amounted to 10 pmol/l (IR-GIP 11 pmol/l). Exendin (9-39) amide abolished the insulin-stimulatory effect of 60 pmol of GLP-1 or of the GLP-1 agonist exendin-4 (0.5 nmol) injected as bolus, respectively. An intravenous bolus injection of 5.94 nmol of exendin (9-39) amide 3 min before enteral glucose infusion grossly reduced the total insulin secretory response (by 60%) and significantly increased circulating blood glucose levels (P < 0.05). In contrast, the GLP-1 antagonist left the insulin response after an intravenous glucose or glucose plus GIP (60 pmol) load unaltered. Our data support the concept that GLP-1 is an important incretin factor. Exendin (9-39) amide is a useful GLP-1 antagonist for in vivo studies.
胰高血糖素样肽1（7-37）/（7-36）酰胺（GLP-1）源自肠道胰高血糖素原的加工过程。它被认为是一种重要的促胰岛素分泌的肠激素。本研究使用艾塞那肽（9-39）酰胺作为GLP-1受体拮抗剂，以评估GLP-1对肠促胰岛素效应的作用。对麻醉大鼠进行十二指肠内输注葡萄糖刺激，以评估GLP-1和胃抑制性多肽（GIP）的最大血浆水平。GLP-1的最大免疫反应性（IR）血浆水平为10 pmol/l（IR-GIP为11 pmol/l）。艾塞那肽（9-39）酰胺分别消除了60 pmol GLP-1或推注注射的GLP-1激动剂艾塞那肽-4（0.5 nmol）的胰岛素刺激作用。在肠内输注葡萄糖前3分钟静脉推注5.94 nmol艾塞那肽（9-39）酰胺，显著降低了总的胰岛素分泌反应（降低60%），并显著提高了循环血糖水平（P<0.05）。相比之下，GLP-1拮抗剂对静脉注射葡萄糖或葡萄糖加GIP（60 pmol）负荷后的胰岛素反应没有影响。我们的数据支持GLP-1是一种重要的肠促胰岛素因子这一概念。艾塞那肽（9-39）酰胺是一种用于体内研究的有用的GLP-1拮抗剂。
