An obese mouse model (Cpefat/Cpefat) that has hyperproinsulinemia and late onset obesity has been described. Cpefat/Cpefat 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 Cpefat/Cpefat mice. In addition, secretion of amidated gastrin in response to inhibition of acid secretion was tested in Cpefat/Cpefat. Both gastric acid and challenged gastrin secretion are reduced in Cpefat/Cpefat mice. We conclude that stomach CPE activity is essential for gastric secretory activity and for challenged gastrin release.
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Identification of incompletely processed potential carboxypeptidase E substrates from CpEfat/CpEfat mice.
Proteomics
January 2001
Departments of Biochemistry and Genetics, Amgen, Thousand Oaks, CA, USA.
In an attempt to identify peptides that may be involved in the obese phenotype observed in CpEfat/CpEfat mice (deficient in Carboxypeptidase E, CpE) samples from fourteen neuroendocrine tissues in wild-type and CpEfat/CpEfat mice were obtained. Peptides were purified from these tissues and potential CpE substrate peptides were enriched using an anhydrotrypsin column that captures peptides with basic C-termini. Bound peptides were subjected to tryptic digestion and followed by liquid chromatography-mass spectrometry analysis.
View Article and Find Full Text PDFCarboxypeptidase E (CPE) deficiency in mice with the fat mutation have reduced stomach function.
Proc Soc Exp Biol Med
January 1999
Department of Surgery, The University of Texas Medical Branch, Galveston, Texas 77555-0725, USA.
An obese mouse model (Cpefat/Cpefat) that has hyperproinsulinemia and late onset obesity has been described. Cpefat/Cpefat 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.
View Article and Find Full Text PDFProinsulin targeting to the regulated pathway is not impaired in carboxypeptidase E-deficient Cpefat/Cpefat mice.
J Biol Chem
October 1997
Laboratoires de Recherche Louis Jeantet, University of Geneva, 1211 Geneva 4, Switzerland.
Sorting of proinsulin from the trans-Golgi network to secretory granules is critical for its conversion to insulin as well as for regulated insulin secretion. The proinsulin sorting mechanism is unknown. Recently, carboxypeptidase E (CPE) was proposed as a sorting receptor for prohormones.
View Article and Find Full Text PDFCarboxypeptidase E activity is deficient in mice with the fat mutation. Effect on peptide processing.
J Biol Chem
November 1996
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Carboxypeptidase E (CPE) is involved in the biosynthesis of many peptide hormones and neurotransmitters. Mice with the fat mutation have previously been found to have a point mutation in the cpe gene, and to have greatly reduced levels of CPE-like enzyme activity in the pituitary and pancreatic islets (Naggert, J. K.
View Article and Find Full Text PDFInduced and spontaneous mutations at Ser202 of carboxypeptidase E. Effect on enzyme expression, activity, and intracellular routing.
J Biol Chem
June 1996
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Carboxypeptidase E (CPE) is involved in peptide processing in the brain and various neuroendocrine tissues. In mice homozygous for the Cpefat mutation, the virtual absence of CPE activity in islets of Langerhans and pituitary was associated with a missense mutation effecting a Ser202 to Pro shift (Naggert, J. K.
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