Intestinal Sensing of Nutrients

Abstract

Ingestion of a meal triggers a range of physiological responses both within and outside the gut, and results in the remote modulation of appetite and glucose homeostasis. Luminal contents are sensed by specialised chemosensitive cells scattered throughout the intestinal epithelium. These enteroendocrine and tuft cells make direct contact with the gut lumen and release a range of chemical mediators, which can either act in a paracrine fashion interacting with neighbouring cells and nerve endings or as classical circulating hormones. At the molecular level, the chemosensory machinery involves multiple and complex signalling pathways including activation of G-protein-coupled receptors and solute carrier transporters. This chapter will discuss our current knowledge of the molecular mechanisms underlying intestinal chemosensation with a particular focus on the relatively well-characterised nutrient-triggered secretion from the enteroendocrine system.

Long-lived intestinal tuft cells serve as colon cancer–initiating cells

“…Consistent with these observations, we found that DCLK1 + cells were largely absent in Ret -/-mice, which lack neuronal innervation of the gut, as well as in extrinsically denervated intestine following small intestinal transplantation. The interaction between epithelial cells and neurons may not be unique to DCLK1 + tuft cells and has, in fact, been suggested in other secretory and enteroendocrine cell types (53). However, a potential nerve/tuft cell axis also appears to be important in intestinal homeostasis, as intestinal proliferation, and thus the state of intestinal progenitors, was found to be highly dependent on neural innervation (52,54).…”

Insulin-like peptide 5 is an orexigenic gastrointestinal hormone

“…Gut hormones have a variety of physiological actions outside the intestine, and play a central role in linking food ingestion to peripheral nutrient disposal and appetite (3,4). Indeed, glucagon-like peptide-1 (GLP-1) analogs and inhibitors of GLP-1 degradation are now widely prescribed for the treatment of type 2 diabetes, offering additional beneficial effects on body weight compared with conventional insulin secretagogues (5,6).…”

Porcine Ex Vivo Intestinal Segment Model

“…These hormones are released following interaction of nutrients and other compounds with G-protein coupled receptors and solute carrier transporters located on enteroendocrine cells. CCK, GLP-1 and PYY are involved in generating satiety and satiation (Gribble 2012 ;Tolhurst et al 2012 ). Enteroendocrine cells are scattered throughout the epithelial layer of the gastrointestinal tract (Tolhurst et al 2012 ).…”

“…CCK, GLP-1 and PYY are involved in generating satiety and satiation (Gribble 2012 ;Tolhurst et al 2012 ). Enteroendocrine cells are scattered throughout the epithelial layer of the gastrointestinal tract (Tolhurst et al 2012 ). Enteroendocrine I-cells mainly release CCK and are relatively abundant in the duodenum, whereas GLP-1 and PYY are released by L-cells mainly present in the distal jejunum, ileum and colon (Holst 2007 ;Iwasaki and Yada 2012 ).…”