Enteroendocrine L cell (revision 7)

Enteroendocrine L cells are specialised epithelial cells distributed throughout the distal small intestine and colon that secrete Glucagon-like peptide-1 (GLP-1) in response to the presence of nutrients in the lumen. They are the source of the majority of circulating GLP-1 and are therefore primary mediators of the incretin effect.^[1]

L cells are open-type endocrine cells — their apical surface is exposed directly to the intestinal lumen, allowing direct contact with nutrients and bacterial metabolites. This arrangement is in contrast to closed-type endocrine cells, which do not face the lumen. The L-cell lineage differentiates from intestinal stem cells under the influence of specific transcription factors including neurogenic regulatory elements.^[2]

L cells are polarised epithelial cells with microvilli on the apical surface and secretory granules in the basolateral cytoplasm. The apical surface, open to the lumen, serves as the nutrient-sensing compartment; the basolateral surface contains receptors and ion channels that relay signals to the secretory machinery. L cells represent approximately 0.5–1% of all intestinal epithelial cells overall but are far more frequent in the ileum and colon than the duodenum.^[2]

L cells express nutrient-sensing receptors including receptors for free fatty acids (particularly for long-chain and short-chain fatty acids), a glucose transporter for apical glucose sensing, and taste receptors. This array of receptors allows L cells to respond to a broad spectrum of luminal contents.^[1]