Intestinal nutrient-sensing pathways

Intestinal nutrient-sensing pathways represent a sophisticated network of receptors and transporters in the gut epithelium that detect dietary macronutrients such as carbohydrates, lipids, and proteins (NIH, 2021). These pathways primarily involve enteroendocrine cells (EECs) which, upon activation by luminal nutrients, secrete key metabolic hormones including glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and cholecystokinin (CCK) (Cambridge University Press, 2020). These hormonal signals, along with neural relays via the gut-brain-liver axis, are essential for regulating postprandial glucose levels, insulin sensitivity, and satiety (Diabetes, 2013). Dysregulation of these sensing mechanisms is a hallmark of metabolic disorders, including obesity and type 2 diabetes, where the gut's ability to signal energy balance is often impaired (Nature, 2015). Pharmacological interventions frequently target specific components of these pathways, such as the GLP-1 receptor or the DPP-4 enzyme, to restore or augment the body's natural metabolic response (Drug Discovery News, 2023). Metformin has also been shown to exert its effects partly through the modulation of intestinal mitochondrial function and subsequent nutrient-sensing signaling (Bioengineer.org, 2024). Emerging therapies also explore direct stimulation of these pathways using targeted delivery systems to restore natural metabolic balance (Aphaia Pharma, 2023). Overall, these pathways represent a critical node in the integration of nutritional intake and systemic energy homeostasis.

Other names

Gut nutrient sensingEnteroendocrine nutrient sensingIntestinal chemosensingGut-brain metabolic axisGut-brain-liver axis

Modulation of enteroendocrine cell signaling to stimulate the release of metabolic hormones and activate gut-brain-liver neural relays for systemic homeostasis.