Secretin potentiates cholinergically induced glucagon secretion in the mouse

Abstract

Glucagon secretion is stimulated by cholinergic activation, and it is known that the polypeptides VIP (vasoactive intestinal polypeptide) and GIP (gastric inhibitory polypeptide) both potentiate this cholinergically induced glucagon secretion. In this study, we investigated whether secretin, which shows structural similarities to both VIP and GIP, affects basal and cholinergically induced glucagon secretion in the mouse. Secretin was injected i.v. to mice at dose levels varying from 0.53 to 17 nmol kg^‐1, and plasma samples were taken at 2, 6 and 10 min following injection. It was found that secretin in this wide dose range did not affect basal glucagon concentrations. When the cholinergic agonist carbachol was injected i.v. at 0.16 μmol kg^‐1, plasma glucagon levels were elevated; at 2 min at 0.84 ± 0.04 ng ml^‐1 compared to 0.31 ± 0.02 ng ml^‐1 in controls(P < 0.001). A combination of carbachol and secretin (4.25 nmol kg^‐1)enhanced plasma glucagon levels to 1.22 ± 0.07 ng ml^‐1. Thus, secretin potentiated carbachol‐induced glucagon secretion by 70% (P < 0.001). Concomitantly, plasma glucose levels were elevated: 10.8 ± 0.4 mmol 1^‐1, compared to 9.2 ± 0.4 mmol 1^‐1 in controls (P < 0.001). We conclude that secretin, while being without effect on basal glucagon secretion, markedly potentiates cholinergically induced glucagon secretion in the mouse, resulting in increased plasma glucose levels.