Effects of helodermin and VIP on insulin and glucagon secretion in the mouse

Helodermin and vasoactive intestinal polypeptide (VIP) are structurally related peptides. We have examined their effects on insulin and glucagon secretion in the mouse. Following intravenous injection, helodermin and VIP equipotently increased plasma glucagon levels with a maximal effect obtained at the dose level of 2 nmol/kg. The maximal response was not augmented by giving the two peptides together at maximal dose levels, showing that helodermin and VIP stimulate glucagon secretion by activating the same mechanisms. Furthermore, both peptides markedly potentiated glucagon secretion stimulated by the cholinergic agonist carbachol, showing that they sensitize glucagon secretion for muscarinic activation. This sensitizing action was abolished by methylatropine, whereas the direct glucagonotropic action of the peptides was insensitive to muscarinic antagonism. Plasma insulin levels were not affected by helodermin but slightly increased by VIP. The study suggests that helodermin and VIP (1) stimulate basal glucagon secretion by the same mechanism, which is insensitive to muscarinic antagonism, (2) sensitize the glucagon secretion for cholinergic activation, and (3) have no or only weak effect on insulin secretion.