Increased glucose-induced secretion of glucagon-like peptide-1 in mice lacking the carcinoembryonic antigenrelated cell adhesion molecule 2 (CEACAM2)

Simona Ghanem, Garrett Heinrich, Sumona G. Lester, Verena Pfeiffer, Sumit Bhattacharya, Payal R. Patel, Anthony M. DeAngelis, Tong Dai, Sadeesh K. Ramakrishnan, Zachary N. Smiley, Dae Y. Jung, Yongjin Lee, Tadahiro Kitamura, Suleyman Ergun, Rohit N. Kulkarni, Jason K. Kim, David R. Giovannucci, Sonia M. Najjar

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 showingCEACAM2expression 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-1release into themediumofGLUTagenteroendocrine cells was increased with siRNA-mediated Ceacam2 downregulation in parallel to an increase in Ca2+ entry through L-type voltage-dependent Ca2+ channels. Thus, CEACAM2 regulates insulin secretion, at least in part, by a GLP-1-mediated mechanism, independent of confounding metabolic factors.

Original languageEnglish
Pages (from-to)980-988
Number of pages9
JournalJournal of Biological Chemistry
Volume291
Issue number2
DOIs
Publication statusPublished - 8 Jan 2016
Externally publishedYes

Fingerprint

Glucagon-Like Peptide 1
Cell Adhesion Molecules
Insulin
Glucose
Incretins
Hyperphagia
Carcinoembryonic Antigen
Clamping devices
Glucose Tolerance Test
Plasma Cells
Somatostatin
Glucagon
Islets of Langerhans
Small Interfering RNA
Fluorescent Antibody Technique
Down-Regulation
Eating
Plasmas
Mutation
Electric potential

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Increased glucose-induced secretion of glucagon-like peptide-1 in mice lacking the carcinoembryonic antigenrelated cell adhesion molecule 2 (CEACAM2). / Ghanem, Simona; Heinrich, Garrett; Lester, Sumona G.; Pfeiffer, Verena; Bhattacharya, Sumit; Patel, Payal R.; DeAngelis, Anthony M.; Dai, Tong; Ramakrishnan, Sadeesh K.; Smiley, Zachary N.; Jung, Dae Y.; Lee, Yongjin; Kitamura, Tadahiro; Ergun, Suleyman; Kulkarni, Rohit N.; Kim, Jason K.; Giovannucci, David R.; Najjar, Sonia M.

In: Journal of Biological Chemistry, Vol. 291, No. 2, 08.01.2016, p. 980-988.

Research output: Contribution to journalArticle

Ghanem, S, Heinrich, G, Lester, SG, Pfeiffer, V, Bhattacharya, S, Patel, PR, DeAngelis, AM, Dai, T, Ramakrishnan, SK, Smiley, ZN, Jung, DY, Lee, Y, Kitamura, T, Ergun, S, Kulkarni, RN, Kim, JK, Giovannucci, DR & Najjar, SM 2016, 'Increased glucose-induced secretion of glucagon-like peptide-1 in mice lacking the carcinoembryonic antigenrelated cell adhesion molecule 2 (CEACAM2)', Journal of Biological Chemistry, vol. 291, no. 2, pp. 980-988. https://doi.org/10.1074/jbc.M115.692582
Ghanem, Simona ; Heinrich, Garrett ; Lester, Sumona G. ; Pfeiffer, Verena ; Bhattacharya, Sumit ; Patel, Payal R. ; DeAngelis, Anthony M. ; Dai, Tong ; Ramakrishnan, Sadeesh K. ; Smiley, Zachary N. ; Jung, Dae Y. ; Lee, Yongjin ; Kitamura, Tadahiro ; Ergun, Suleyman ; Kulkarni, Rohit N. ; Kim, Jason K. ; Giovannucci, David R. ; Najjar, Sonia M. / Increased glucose-induced secretion of glucagon-like peptide-1 in mice lacking the carcinoembryonic antigenrelated cell adhesion molecule 2 (CEACAM2). In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 2. pp. 980-988.
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AU - Pfeiffer, Verena

AU - Bhattacharya, Sumit

AU - Patel, Payal R.

AU - DeAngelis, Anthony M.

AU - Dai, Tong

AU - Ramakrishnan, Sadeesh K.

AU - Smiley, Zachary N.

AU - Jung, Dae Y.

AU - Lee, Yongjin

AU - Kitamura, Tadahiro

AU - Ergun, Suleyman

AU - Kulkarni, Rohit N.

AU - Kim, Jason K.

AU - Giovannucci, David R.

AU - Najjar, Sonia M.

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