Carboxypeptidase E (CPE) deficiency in mice with the fat mutation have reduced stomach function

An obese mouse model (Cpe(fat)/Cpe(fat)) that has hyperproinsulinemia and late onset obesity has been described. Cpe(fat)/Cpe(fat) mice have a missense mutation in carboxypeptidase E (CPE), a processing enzyme essential for production of biologically active endocrine and neuroendocrine peptides. We have reported previously that CPE activity was absent in the antrum of the stomach and that processing of progastrin to the amidated biologically active form of gastrin is reduced. Since gastrin is a major secretagogue for gastric acid secretion, the purpose of the present experiments was to examine gastric acid secretion in Cpe(fat)/Cpe(fat) mice. In addition, secretion of amidated gastrin in response to inhibition of acid secretion was tested in Cpe(fat)/Cpe(fat). Both gastric acid and challenged gastrin secretion are reduced in Cpe(fat)/Cpe(fat) mice. We conclude that stomach CPE activity is essential for gastric secretory activity and for challenged gastrin release.