Suzuki S, Kawai K, Ohashi S, Mukai H, Yamashita K
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Japan.
Endocrinology. 1989 Dec;125(6):3109-14. doi: 10.1210/endo-125-6-3109.
Truncated glucagon-like peptide-1 (GLP-1) possesses a potent stimulatory activity for insulin secretion and a slight inhibiting activity for glucagon secretion. The aim of this paper is to examine the activities of N- and C-terminal fragments of GLP-1 using a rat pancreas perfusion system. Concerning the N-terminal portion, GLP-1(7-37) amide elicited a clear insulinotropic activity at 0.1 or 1 nM with the perfusate containing 5.5 mM glucose and 5 mM arginine, while 10 nM GLP-1-(1-37) amide, -(6-37) amide, and -(8-37) amide did not. Concerning the C-terminal portion, GLP-1-(7-37) amide, -(7-37), and -(7-36) amide had a similar potency of insulinotropic activity, and GLP-1-(7-35) was less potent; 0.1 nM GLP-1-(7-35) did not stimulate insulin release, nor did 10 nM GLP-1-(7-20). Glucagon release was significantly suppressed by 1 and 10 nM GLP-1-(7-37) amide, 10 nM GLP-1-(7-37), and 1 nM GLP-1-(7-36) amide. Other fragment peptides of GLP-1, including GLP-1-(7-35), had no effect. From these results it is concluded that histidine at position 7 of GLP-1 as a free N-terminal amino acid is very important in GLP-1's insulinotropic activity and probably in glucagon-inhibiting activity, and that C-terminal amidation and three C-terminal amino acids are less important for these activities.
截短的胰高血糖素样肽-1（GLP-1）对胰岛素分泌具有强大的刺激活性，对胰高血糖素分泌具有轻微的抑制活性。本文旨在使用大鼠胰腺灌注系统研究GLP-1的N端和C端片段的活性。关于N端部分，在含有5.5 mM葡萄糖和5 mM精氨酸的灌注液中，0.1或1 nM的GLP-1(7-37)酰胺可引发明显的促胰岛素活性，而10 nM的GLP-1-(1-37)酰胺、-(6-37)酰胺和-(8-37)酰胺则无此作用。关于C端部分，GLP-1-(7-37)酰胺、-(7-37)和-(7-36)酰胺具有相似的促胰岛素活性效力，而GLP-1-(7-35)的效力较低；0.1 nM的GLP-1-(7-35)不刺激胰岛素释放，10 nM的GLP-1-(7-20)也无此作用。1和10 nM的GLP-1-(7-37)酰胺、10 nM的GLP-1-(7-37)和1 nM的GLP-1-(7-36)酰胺可显著抑制胰高血糖素释放。GLP-1的其他片段肽，包括GLP-1-(7-35)，则无此作用。从这些结果可以得出结论，GLP-1第7位的组氨酸作为游离N端氨基酸对GLP-1的促胰岛素活性非常重要，可能对胰高血糖素抑制活性也很重要，并且C端酰胺化和三个C端氨基酸对这些活性不太重要。
