Classification and functions of enteroendocrine cells of the lower gastrointestinal tract

Abstract

With over thirty different hormones identified as being produced in the gastrointestinal (GI) tract, the gut has been described as 'the largest endocrine organ in the body' (Ann. Oncol., 12, 2003, S63). The classification of these hormones and the cells that produce them, the enteroendocrine cells (EECs), has provided the foundation for digestive physiology. Furthermore, alterations in the composition and function of EEC may influence digestive physiology and thereby associate with GI pathologies. Whilst there is a rapidly increasing body of data on the role and function of EEC in the upper GI tract, there is a less clear-cut understanding of the function of EEC in the lower GI. Nonetheless, their presence and diversity are indicative of a role. This review focuses on the EECs of the lower GI where new evidence also suggests a possible relationship with the development and progression of primary adenocarcinoma.

Figure 1

Development of enteroendocrine cells of the gastrointestinal tract. As daughter cells of the pluripotent stem cells migrate from the base of the crypt towards the surface epithelial cuff, they commit to one of the four cellular lineages. Enteroendocrine cell-committed differentiating cells migrate slowly in comparison with differentiating cells of the goblet and enterocyte lineages. Paneth cell-committed differentiating cells migrate towards the base of the crypts as they mature.

Figure 2

Distribution of enteroendocrine cell subtypes. Enterochromaffin cells are the most abundant enteroendocrine cell subtype of the colon and rectum. D cells are uncommon although scattered evenly throughout the gastrointestinal tract. L cells are uncommon proximal to the terminal ileum, and their frequency increases from proximal to distal being most concentrated in the rectum.

Figure 3

Processing of proglucagon. Alternative post-transcriptional splicing of the proglucagon precursor molecule is into glicentin, GLP-1, GLP-2 and oxyntomodulin in intestinal L cells and into pancreatic glucagon in pancreatic alpha cells. GLP-1, glucagon-like peptide 1; GLP-2, glucagon-like peptide 2. Adapted from Holst (2007).