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Updated: May 14, 2026

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
Carcinoembryonic antigen-related cell adhesion molecule 2 controls energy balance and peripheral insulin action in
Garrett Heinrich1, Sumona Ghosh, Anthony M Deangelis
1The Center for Diabetes and Endocrine Research, Department of Physiology & Pharmacology, College of Medicine, University of Toledo, Health Science Campus, Toledo, Ohio 43614, USA.
Background & Aims:
The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a transmembrane glycoprotein with pleotropic functions, including clearance of hepatic insulin. We investigated the functions of the related protein CEACAM2, which has tissue-specific distribution (kidney, uterus, and crypt epithelia of intestinal tissues), in genetically modified mice.
Methods:
Ceacam2-null mice (Cc2-/-) were generated from a 129/SvxC57BL/6J background. Female mice were assessed by hyperinsulinemic-euglycemic clamp analysis and indirect calorimetry and body fat composition was measured. Cc2-/- mice and controls were fed as pairs, given insulin tolerance tests, and phenotypically characterized.
Results:
Female, but not male Cc2-/- mice exhibited obesity that resulted from hyperphagia and reduced energy expenditure. Pair feeding experiments showed that hyperphagia led to peripheral insulin resistance. Insulin action was normal in liver but compromised in skeletal muscle of female Cc2-/- mice; the mice had incomplete fatty acid oxidation and impaired glucose uptake and disposal. The mechanism of hyperphagia in Cc2-/- mice is not clear, but appears to result partly from increased hyperinsulinemia-induced hypothalamic fatty acid synthase levels and activity. Hyperinsulinemia was caused by increased insulin secretion.
Conclusions:
In mice, CEACAM2 is expressed by the hypothalamus. Cc2-/- mice develop obesity from hyperphagia and reduced energy expenditure, indicating its role in regulating energy balance and insulin sensitivity.
Insights
Carcinoembryonic antigen-related cell adhesion molecule 2 (CEACAM2) deficiency in mice causes obesity due to increased appetite and lower energy use. This highlights CEACAM2
Area of Science:
- Endocrinology
- Metabolism
- Molecular Biology
Background:
- Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) influences hepatic insulin clearance.
- CEACAM2 is a related protein with a specific tissue distribution.
- The physiological roles of CEACAM2 remain largely uncharacterized.
Purpose of the Study:
- To investigate the function of CEACAM2 in regulating energy balance and insulin sensitivity.
- To characterize the phenotype of CEACAM2-deficient mice.
Main Methods:
- Generation of Ceacam2-null (Cc2-/-) mice.
- Phenotypic characterization including hyperinsulinemic-euglycemic clamp analysis, indirect calorimetry, and body composition analysis.
- Pair feeding and insulin tolerance tests were performed.
Main Results:
- Female Cc2-/- mice developed obesity, hyperphagia, and reduced energy expenditure.
- Hyperphagia contributed to peripheral insulin resistance, particularly in skeletal muscle.
- Impaired fatty acid oxidation and glucose disposal were observed in skeletal muscle.
- Increased hypothalamic fatty acid synthase and hyperinsulinemia were implicated in hyperphagia.
Conclusions:
- CEACAM2 is expressed in the mouse hypothalamus.
- CEACAM2 plays a crucial role in regulating energy balance and insulin sensitivity.
- CEACAM2 deficiency leads to obesity through hyperphagia and altered energy expenditure.
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