Evidence that glucagon stimulates insulin secretion through its own receptor in rats.
Since glucagon-like peptide-1 (7-36) amide (7-37) (GLP-1) has been found to be a potent insulinotropic hormone, it has been postulated that glucagon stimulates insulin secretion from islet beta cells through the GLP-1 receptor. We therefore examined the effects of a GLP-1 receptor antagonist, exendin (9-39) amide, on glucagon- or GLP-1-stimulated insulin release from isolated perfused rat pancreas. When infusion of 100 nmol/l exendin (9-39) amide was started 5 min before that of 1 nmol/l glucagon, the stimulation of insulin release by glucagon was similar to that found in the control situation (preinfusion with vehicle alone). By contrast, when 0.3 nmol/l GLP-1 was used in the same experimental setting, exendin (9-39) amide clearly inhibited insulin release. These results indicate that glucagon stimulates insulin release mainly through glucagon receptors but not GLP-1 receptors on islet beta cells.
Kawai
K
K
Department of Internal Medicine, University of Tsukuba, Japan.
Yokota
C
C
Ohashi
S
S
Watanabe
Y
Y
Yamashita
K
K
D000818:Animals; D005934:Glucagon / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010477:Perfusion; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors; D014688:Venoms / Q000494:pharmacology
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; D014688:Venoms; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D005934:Glucagon