Comparison of the effects of various C-terminal and N-terminal fragment peptides of glucagon-like peptide-1 on insulin and glucagon release from the isolated perfused rat pancreas

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glucagon / metabolism*
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides
  • Histidine
  • Insulin / metabolism*
  • Insulin Secretion
  • Male
  • Pancreas / drug effects
  • Pancreas / metabolism*
  • Peptide Fragments / pharmacology*
  • Peptides / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship


  • Insulin
  • Peptide Fragments
  • Peptides
  • glucagon-like peptide 1 (7-36)amide
  • Histidine
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon
  • glucagon-like peptide 1 (7-37)