Attenuated processing of proglucagon and glucagon-like peptide-1 in carboxypeptidase E-deficient mice

The maturation of many peptide hormones is attenuated in carboxypeptidase E (CPE)-deficient fat/fat mice, leading to a slowly developing, adult-onset obesity with mild diabetes. To determine the contribution of tile hormones generated from the proglucagon precursor to this phenotype, we studied the tissue-specific processing of glucagon and glucagon-like peptide-1 (GLP-1) in these mice. In all tissues examined there was a great reduction in matur e amidated GLP-1. Furthermore, a lack of CPE attenuates prohormone converta se processing of proglucagon in both the pancreas and the intestine, These findings suggest that defects in proglucagon processing together with other endocrine malfunctions could contribute to the diabetic and obesity phenot ype in fat/fat mice.