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 fou nd to be a potent insulinotropic hormone, it has been postulated that glucagon stimulates insulin secretion from islet beta cells through th e GLP-1 receptor. We therefore examined the effects of a GLP-1 recepto r antagonist, exendin (9-39) amide, on glucagon- or GLP-1-stimulated i nsulin release from isolated perfused rat pancreas. When infusion of 1 00 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 simila r to that found in the control situation (preinfusion with vehicle alo ne), By contrast, when 0.3 nmol/l GLP-1 was used in the same experimen tal setting, exendin (9-39) amide clearly inhibited insulin release. T hese results indicate that glucagon stimulates insulin release mainly through glucagon receptors but not GLP-1 receptors on islet beta cells .