HYPERPROINSULINAEMIA IN OBESE FAT FAT MICE ASSOCIATED WITH A CARBOXYPEPTIDASE-E MUTATION WHICH REDUCES ENZYME-ACTIVITY/

Citation
Jk. Naggert et al., HYPERPROINSULINAEMIA IN OBESE FAT FAT MICE ASSOCIATED WITH A CARBOXYPEPTIDASE-E MUTATION WHICH REDUCES ENZYME-ACTIVITY/, Nature genetics, 10(2), 1995, pp. 135-142
Citations number
41
Categorie Soggetti
Genetics & Heredity
Journal title
ISSN journal
10614036
Volume
10
Issue
2
Year of publication
1995
Pages
135 - 142
Database
ISI
SICI code
1061-4036(1995)10:2<135:HIOFFM>2.0.ZU;2-V
Abstract
Mice homozygous for the fat mutation develop obesity and hyperglycaemi a that can be suppressed by treatment with exogenous insulin. The fat mutation maps to mouse chromosome 8, very close to the gene for carbox ypeptidase E (Cpe), which encodes an enzyme (CPE) that processes proho rmone intermediates such as proinsulin. We now demonstrate a defect in proinsulin processing associated with the virtual absence of CPE acti vity in extracts of fat/fat pancreatic islets and pituitaries. A singl e Ser202Pro mutation distinguishes the mutant Cpe allele, and abolishe s enzymatic activity in vitro. Thus, the fat mutation represents the f irst demonstration of an obesity-diabetes syndrome elicited by a genet ic defect in a prohormone processing pathway.