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http://purl.uniprot.org/citations/18544705http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18544705http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18544705http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Liver-specific inactivation of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) by a dominant-negative transgene (l-SACC1 mice) impaired insulin clearance, caused insulin resistance, and increased hepatic lipogenesis. To discern whether this phenotype reflects a physiological function of CEACAM1 rather than the effect of the dominant-negative transgene, we characterized the metabolic phenotype of mice with null mutation of the Ceacam1 gene (Cc1(-/-)).

Research design and methods

Mice were originally generated on a mixed C57BL/6x129sv genetic background and then backcrossed 12 times onto the C57BL/6 background. More than 70 male mice of each of the Cc1(-/-) and wild-type Cc1(+/+) groups were subjected to metabolic analyses, including insulin tolerance, hyperinsulinemic-euglycemic clamp studies, insulin secretion in response to glucose, and determination of fasting serum insulin, C-peptide, triglyceride, and free fatty acid levels.

Results

Like l-SACC1, Cc1(-/-) mice exhibited impairment of insulin clearance and hyperinsulinemia, which caused insulin resistance beginning at 2 months of age, when the mutation was maintained on a mixed C57BL/6x129sv background, but not until 5-6 months of age on a homogeneous inbred C57BL/6 genetic background. Hyperinsulinemic-euglycemic clamp studies revealed that the inbred Cc1(-/-) mice developed insulin resistance primarily in liver. Despite substantial expression of CEACAM1 in pancreatic beta-cells, insulin secretion in response to glucose in vivo and in isolated islets was normal in Cc1(-/-) mice (inbred and outbred strains).

Conclusions

Intact insulin secretion in response to glucose and impairment of insulin clearance in l-SACC1 and Cc1(-/-) mice suggest that the principal role of CEACAM1 in insulin action is to mediate insulin clearance in liver."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.org/dc/terms/identifier"doi:10.2337/db08-0379"xsd:string
http://purl.uniprot.org/citations/18544705http://purl.org/dc/terms/identifier"doi:10.2337/db08-0379"xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Dai T."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Dai T."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Lee S.J."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Lee S.J."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Kim J.K."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Kim J.K."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Heinrich G."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Heinrich G."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Kulkarni R.N."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Kulkarni R.N."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Najjar S.M."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Najjar S.M."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Assmann A."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Assmann A."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Bowman T.A."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Bowman T.A."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"DeAngelis A.M."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"DeAngelis A.M."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Hong E.G."xsd:string
http://purl.uniprot.org/citations/18544705http://purl.uniprot.org/core/author"Hong E.G."xsd:string
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