Ohneda A, Ohneda K, Ohneda M, Koizumi F, Ohashi S, Kawai K, Suzuki S
Health Center, Tohoku University, Sendai.
Tohoku J Exp Med. 1991 Nov;165(3):209-21. doi: 10.1620/tjem.165.209.
In order to clarify the relationship between the structure and function of glucagon-like peptide (GLP) 1 in the endocrine function of the pancreas, the response of insulin and glucagon to various synthetic GLP-1-related peptides was investigated in anesthetized dogs. GLP-1-related peptides were administered in a dosage of 400 pmol within 10 min into the pancreatic artery during glucose or arginine infusion and the changes in plasma insulin and glucagon in the pancreatic vein were studied. GLP-1 (7-36) and (7-37), as well as glucagon enhanced insulin release during glucose infusion, whereas neither GLP-1 (1-37), (7-20), (6-37) nor (8-37) stimulated insulin release. The administration of GLP-1 (1-37), (7-36) and (7-37) reduced glucagon release during glucose infusion. When arginine was infused, GLP-1 (7-20), (7-36), (7-37), and glucagon enhanced insulin release. In contrast, glucagon release was increased by the administration of GLP-1 (7-20), (8-37), and (7-37). The present study indicates that histidine at the 7th position of GLP-1 is important in eliciting biological action and that only truncated GLP-1 (7-36), (7-37), and (7-20) showed an insulinotropic action as strong as glucagon in dogs. Furthermore, it is suggested that the response of insulin and glucagon to GLP-1-related peptides is dependent on a background condition.
为了阐明胰高血糖素样肽（GLP）-1的结构与功能在胰腺内分泌功能中的关系，研究了麻醉犬体内胰岛素和胰高血糖素对各种合成的GLP-1相关肽的反应。在输注葡萄糖或精氨酸期间，将GLP-1相关肽以400 pmol的剂量在10分钟内注入胰腺动脉，并研究胰腺静脉中血浆胰岛素和胰高血糖素的变化。GLP-1（7-36）和（7-37）以及胰高血糖素在输注葡萄糖期间增强胰岛素释放，而GLP-1（1-37）、（7-20）、（6-37）和（8-37）均未刺激胰岛素释放。GLP-1（1-37）、（7-36）和（7-37）的给药在输注葡萄糖期间减少了胰高血糖素释放。当输注精氨酸时，GLP-1（7-20）、（7-36）、（7-37）和胰高血糖素增强胰岛素释放。相反，GLP-1（7-20）、（8-37）和（7-37）的给药增加了胰高血糖素释放。本研究表明，GLP-1第7位的组氨酸在引发生物学作用中很重要，并且在犬中只有截短的GLP-1（7-36）、（7-37）和（7-20）表现出与胰高血糖素一样强的促胰岛素作用。此外，提示胰岛素和胰高血糖素对GLP-1相关肽的反应取决于背景条件。
