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

Age-dependent insulin resistance in male mice with null deletion of the carcinoembryonic antigen-related cell adhesion molecule 2 gene

“…CEACAM2 is expressed in kidney, spleen, testis and platelets in addition to the crypt cells and the villi lining of the intestinal segment beginning with distal jejunum [6–12]. It is also expressed in the hypothalamus, including the ventromedial hypothalamus (VMH), and other brain centres involved in feeding behaviour, including hippocampus, striatum, olfactory bulb and the globus and ventral pallidus [6, 13, 14].…”

“…Whereas CEACAM2 is detected in pancreatic cells, in particular in non-beta cells, its null deletion does not influence basal plasma levels of hormones (insulin, glucagon and somatostatin), nor does it affect islet areas or glucose-induced insulin secretion in pooled Cc2 −/− islets [12]. Instead, CEACAM2 promotes glucose-stimulated insulin secretion.…”

“…Instead, CEACAM2 promotes glucose-stimulated insulin secretion. This is mediated at least in part via a mechanism dependent on glucagon-like peptide-1 (GLP-1), consistent with its expression in the distal intestinal villi [12]. In addition to its role in metabolism, CEACAM2 regulates spermatid maturation [7, 16] and platelet activation and adhesion [8].…”

“…This notion is supported by the induction of brain CEACAM2 production that occurs at fasting and its suppression at refeeding [6]. Studies in GLUTag entero-endocrine cells revealed that glucose, but not insulin, rapidly suppresses Cc2 mRNA level at refeeding [12]. …”

“…In contrast, it fails to trigger insulin resistance in male mutants up to 7 months of age [12, 15], probably because of the differential hypermetabolic state in relation to activated sympathetic tone regulation of white adipose tissue (WAT) and increased spontaneous activity in male mutants [15]. Cc2 −/− male mice remain lean and insulin sensitive until 7–8 months of age, as demonstrated by hyperinsulinaemic–euglycaemic clamp analysis [12]. They also manifest elevated glucose-induced glucagon-like peptide 1 (GLP-1)-mediated insulin secretion with preserved beta cell insulin secretory function at this age, as shown by hyperglycaemic clamp analysis [12].…”