Insulin and glucagon secretion in the rat: effects of gastrin releasing peptide

Immunoreactive gastrin releasing peptide (GRP) has been shown to occur in intrapancreatic nerve fibers, and to be released from the perfused porcine pancreas during electrical vagal activation. Hence, it could be anticipated that GRP may be of functional importance for the neural control of islet hormone secretion. Therefore, we investigated the effects of intravenous infusion of GRP on basal and stimulated insulin and glucagon secretion in vivo in the rat. We found that GRP, at 4.3 or 17 pmol/min, increased basal plasma concentrations of both insulin and glucagon and induced hyperglycemia. Furthermore, GRP (1.1 or 4.3 pmol/min) potentiated the plasma insulin response to glucose (7 mg/min). In contrast, the peptide (at 4.3 pmol/min) inhibited the insulin response to arginine (8.5 mg/min). Moreover, GRP increased the plasma glucagon levels during infusion of both arginine and glucose. In summary, in the rat GRP 1) stimulates basal insulin and glucagon secretion, 2) potentiates glucose-stimulated insulin secretion, 3) inhibits arginine-stimulated insulin secretion, 4) potentiates arginine-stimulated glucagon secretion, 5) counteracts the glucose-induced suppression of glucagon secretion, and 6) induces hyperglycemia. Though this study can not establish the mechanisms or physiological importance of these effects, we conclude that the intrapancreatic neuropeptide GRP has the capability to affect both insulin and glucagon secretion in vivo in the rat.