Gastrin releasing peptide (GRP): effects on basal and stimulated insulin and glucagon secretion in the mouse.
GRP is a pancreatic neuropeptide and may be of importance for the neural control of insulin and glucagon secretion. In this study, we investigated the effects of GRP on basal and stimulated insulin and glucagon secretion in the mouse. Intravenous injections of GRP at dose levels exceeding 2.12 nmol/kg were found to rapidly increase basal plasma levels of both insulin and glucagon. Furthermore, at a low dose level without effect on basal plasma insulin levels, GRP was found to potentiate the insulin response to both glucose (by 40%; p less than 0.05) and to the cholinergic agonist carbachol (by 57%; p less than 0.01). Also, GRP was at this dose level found to potentiate the glucagon response to carbachol (p less than 0.01). Glucose abolished GRP-induced glucagon secretion. Moreover, methylatropine given at a dose level that totally abolishes carbachol-induced insulin secretion inhibited GRP-induced insulin secretion by 39% (p less than 0.05) and GRP-induced glucagon secretion by 25% (p less than 0.01). L-Propranolol at a dose level that totally abolishes beta-adrenergically-induced insulin secretion inhibited GRP-induced insulin secretion by 52% (p less than 0.01) and GRP-induced glucagon secretion by 15% (p less than 0.05). In summary, we have shown that GRP stimulates basal and potentiates stimulated insulin and glucagon secretion in mice, and that the stimulatory effects of GRP on insulin and glucagon secretion are partially inhibited by muscarinic blockade by methylatropine or by beta-adrenoceptor blockade by propranolol. We conclude that GRP activates potently both insulin and glucagon secretion in the mouse by mechanisms that are partially related to the muscarinic and the beta-adrenergic receptors.
D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D019886:Gastrin-Releasing Peptide; D005934:Glucagon / Q000097:blood*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000097:blood*; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology
D001286:Atropine Derivatives; D001786:Blood Glucose; D007328:Insulin; D010455:Peptides; D019886:Gastrin-Releasing Peptide; C006649:methylatropine; D002217:Carbachol; D005934:Glucagon; D011433:Propranolol; D005947:Glucose