Comparison of the Effects of Glucagon-Like Peptide-1-( 1-3 7) and -(7-37) and Glucagon on Islet Hormone Release from Isolated Perfused Canine and Rat Pancreases*

Abstract

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 < 0.05); 724 .+-. 129% vs. 311 .+-. 33% of the basal level for somatostatin (P < 0.01)]. GLP-1-(1-37) (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-(1-37), 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.