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.
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.
Suzuki
S
S
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Japan.
Kawai
K
K
Ohashi
S
S
Mukai
H
H
Yamashita
K
K
D000818:Animals; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006639:Histidine; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; C055453:glucagon-like peptide 1 (7-36)amide; D006639:Histidine; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; C051322:glucagon-like peptide 1 (7-37)