Neuropeptide Y and Calcitonin Gene-Related Peptide: Effects on Glucagon and Insulin Secretion in the Mouse

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Abstract
Neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) are both intrapancreatic neuropeptides that are known to inhibit stimulated insulin secretion. In the present study, we examined their influences on basal and stimulated glucagon and insulin secretion in the mouse. Either NPY or CGRP was injected intravenously at two dose levels (0.85 or 4.25 nmol/kg). When injected alone, neither of them did affect basal plasma glucagon levels but CGRP reduced basal plasma insulin levels. Glucagon secretion stimulated by the cholinergic agonist carbachol was modestly inhibited by NPY at 4.25 nmol/kg (P2-adrenoceptor agonist terbutaline was markedly inhibited by NPY already at the lower dose level (P<0.01) and potentiated by CGRP (P<0.01). Insulin secretion stimulated by carbachol was inhibited by CGRP (P<0.01) but not affected by NPY, whereas terbutaline-induced insulin secretion was inhibited by both NPY (P<0.05) and CGRP (P<0.01). We conclude that the two intrapancreatic neuropeptides NPY and CGRP have opposite actions on stimulated glucagon secretion in the mouse: NPY in an inhibitory and CGRP in a potentiatory direction. Both peptides, however, inhibit insulin secretion stimulated by terbutaline.