Luminal Chemosensory Cells in the Small Intestine

Abstract

In addition to the small intestine's well-known function of nutrient absorption, the small intestine also plays a major role in nutrient sensing. Similar to taste sensors seen on the tongue, GPCR-coupled nutrient sensors are expressed throughout the intestinal epithelium and respond to nutrients found in the lumen. These taste receptors respond to specific ligands, such as digested carbohydrates, fats, and proteins. The activation of nutrient sensors in the intestine allows for the induction of signaling pathways needed for the digestive system to process an influx of nutrients. Such processes include those related to glucose homeostasis and satiety. Defects in intestinal nutrient sensing have been linked to a variety of metabolic disorders, such as type 2 diabetes and obesity. Here, we review recent updates in the mechanisms related to intestinal nutrient sensors, particularly in enteroendocrine cells, and their pathological roles in disease. Additionally, we highlight the emerging nutrient sensing role of tuft cells and recent work using enteroids as a sensory organ model.

Keywords: GPCR; enteroendocrine cell; enteroid; small intestine; tuft cell.

Figure 1

A schematic diagram of nutrient sensor signaling in an enteroendocrine cell. AA, amino acid; AC; adenylyl cyclase; cAMP, cyclic adenosine monophosphate; CaSR, calcium sensing receptor; DAG, diacylglycerol; FFAR, free fatty acid receptor; GPR119, G-protein receptor 119; IP3, inositol trisphosphate; LCFA, long chain fatty acid; PKA, protein kinase A; PKC protein kinase C; PLC, phospholipase C; PLCβ2, phospholipase C β2; SCFA, short chain fatty acid; SGLT1, sodium/glucose cotransporter 1; TAS1R, taste 1 receptor; TPRM5, transient receptor potential cation channel subfamily M member 5.

Figure 2

Tuft cell morphology in mouse small intestine. Widely used tuft cell markers, F-actin (phalloidin), DCLK1, and acetylated tubulin demonstrate the microvillus structure, whole-cell shape, and dense microtubules, respectively.

Figure 3

Immunostaining for human intestinal tuft cells. Both ChAT and POU2F3 are detected in tuft cells in jejunum paraffin sections. Scale bar: 20 µm.