Comparison of the effects of glucagon-like peptide-1-(1-37) and -(7-37) and glucagon on islet hormone release from isolated perfused canine and rat pancreases.
Recently, it has been demonstrated that glucagon-like peptide-1 (GLP-1)-(7-37) possesses a potent insulinotropic activity. In this paper, we compared the effects of GLP-1-(1-37) and -(7-37) and glucagon on insulin, glucagon, and somatostatin release from isolated perfused canine and rat pancreases under the perfusate condition of 5.5 mM glucose plus arginine. With canine pancreas perfusion, 1 nM GLP-1-(7-37) was more potent in stimulating insulin and somatostatin release than was the same dose of glucagon [stimulation to 375 +/- 36% vs. 302 +/- 28% of the basal level for insulin (P less than 0.05); 724 +/- 129% vs. 311 +/- 33% of the basal level for somatostatin (P less than 0.01)]. GLP-1-(1-37) (1 nM) did not stimulate either insulin or somatostatin release. GLP-1-(7-37) (1 nM) decreased the glucagon level of the effluent perfusate to 67.2 +/- 3.4% of its basal level; but 1 nM GLP-1-(1-37) did not. Glucagon (1 nM) decreased GLP-1-like immunoreactivity to 64.0 +/- 5.2% of its basal level. With rat pancreatic perfusion, the minimal dose for stimulation of insulin release was 100 nM for GLP-1-(1-37), 0.1 nM for GLP-1-(7-37), and 1 nM for glucagon, respectively. Glucagon release was partially inhibited by 100 nM GLP-1-(1-37) and 1 and 10 nM GLP-1-(7-37). The present results indicate that 1) since GLP-1-(7-37) is released from the intestine, it might be an important incretin candidate along with gastric inhibitory peptide; and 2) the release of proglucagon-derived peptides from pancreatic A-cells is regulated by autofeedback through glucagon and GLP-1.
Kawai
K
K
Department of Internal Medicine, University of Tsukuba, Ibaraki-ken, Japan.
Suzuki
S
S
Ohashi
S
S
Mukai
H
H
Ohmori
H
H
Murayama
Y
Y
Yamashita
K
K
D000818:Animals; D002469:Cell Separation; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D010446:Peptide Fragments; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism
D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D013004:Somatostatin; D004763:Glucagon-Like Peptides; C055968:glucagon-like peptide 1 (1-37); D052216:Glucagon-Like Peptide 1; D005934:Glucagon; C051322:glucagon-like peptide 1 (7-37)