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J Biol Chem. 2016 Jan 8;291(2):980-8. doi: 10.1074/jbc.M115.692582. Epub 2015 Nov 19.

Increased Glucose-induced Secretion of Glucagon-like Peptide-1 in Mice Lacking the Carcinoembryonic Antigen-related Cell Adhesion Molecule 2 (CEACAM2).

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From the Center for Diabetes and Endocrine Research and Departments of Physiology and Pharmacology and.
the Institut für Anatomie und Zellbiologie, Universität Würzburg, D-97070 Würzburg, Germany.
Neurosciences, College of Medicine and Life Sciences, University of Toledo, Health Science Campus, Toledo, Ohio 43614.
the Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
the Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, 371-8512 Gunma, Japan, and.
the Islet Cell and Regenerative Biology, Joslin Diabetes Center and Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215.
From the Center for Diabetes and Endocrine Research and Departments of Physiology and Pharmacology and


Carcinoembryonic antigen-related cell adhesion molecule 2 (CEACAM2) regulates food intake as demonstrated by hyperphagia in mice with the Ceacam2 null mutation (Cc2(-/-)). This study investigated whether CEACAM2 also regulates insulin secretion. Ceacam2 deletion caused an increase in β-cell secretory function, as assessed by hyperglycemic clamp analysis, without affecting insulin response. Although CEACAM2 is expressed in pancreatic islets predominantly in non-β-cells, basal plasma levels of insulin, glucagon and somatostatin, islet areas, and glucose-induced insulin secretion in pooled Cc2(-/-) islets were all normal. Consistent with immunofluorescence analysis showing CEACAM2 expression in distal intestinal villi, Cc2(-/-) mice exhibited a higher release of oral glucose-mediated GLP-1, an incretin that potentiates insulin secretion in response to glucose. Compared with wild type, Cc2(-/-) mice also showed a higher insulin excursion during the oral glucose tolerance test. Pretreating with exendin(9-39), a GLP-1 receptor antagonist, suppressed the effect of Ceacam2 deletion on glucose-induced insulin secretion. Moreover, GLP-1 release into the medium of GLUTag enteroendocrine cells was increased with siRNA-mediated Ceacam2 down-regulation in parallel to an increase in Ca(2+) entry through L-type voltage-dependent Ca(2+) channels. Thus, CEACAM2 regulates insulin secretion, at least in part, by a GLP-1-mediated mechanism, independent of confounding metabolic factors.


CEACAM2; GLP-1; diabetes; enteroendocrine cells; gene knock-out; insulin clearance; insulin resistance; insulin secretion; intestine

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