CEACAM2 in GLP-1 Secretion [Metabolism]

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 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.

Source: Journal of Biological Chemistry - January 8, 2016 Category: Chemistry Authors: Ghanem, S. S., Heinrich, G., Lester, S. G., Pfeiffer, V., Bhattacharya, S., Patel, P. R., DeAngelis, A. M., Dai, T., Ramakrishnan, S. K., Smiley, Z. N., Jung, D. Y., Lee, Y., Kitamura, T., Ergun, S., Kulkarni, R. N., Kim, J. K., Giovannucci, D. R., Najjar Tags: Metabolism Source Type: research