Enteroendocrine L-cell nutrient sensing pathways

Enteroendocrine L-cell nutrient sensing pathways represent the integrated molecular systems through which specialized intestinal cells detect dietary intake and regulate metabolic homeostasis [2, 3]. These pathways involve a diverse array of sensors, including G protein-coupled receptors (GPCRs) such as GPR119, FFAR1 (GPR40), FFAR4 (GPR120), and TGR5 (GPBAR1), as well as nutrient transporters like the sodium-glucose co-transporter 1 (SGLT1) [2, 4]. Upon activation by luminal nutrients—including glucose, long-chain fatty acids, and amino acids—these sensors trigger intracellular signaling cascades that lead to the secretion of the incretin hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) [4, 5]. These hormones are vital for enhancing glucose-dependent insulin secretion, slowing gastric emptying, and promoting satiety [2, 4]. Dysregulation of these sensing mechanisms is a hallmark of metabolic disorders such as type 2 diabetes and obesity, where the postprandial incretin response is often blunted [1, 2]. Pharmacological strategies targeting these pathways, such as GPR119 agonists or TGR5 modulators, aim to restore or enhance endogenous hormone release to improve glycemic control and support weight management [2, 4]. This approach offers a potential therapeutic alternative to exogenous GLP-1 receptor agonists by leveraging the body's natural hormone production mechanisms [2].

Other names

L-cell nutrient sensingIncretin secretion pathwaysGut nutrient sensing mechanismsEnteroendocrine nutrient sensing

Activation of G protein-coupled receptors (GPR119, FFAR1, FFAR4, TGR5) and nutrient transporters (SGLT1) on the L-cell membrane, triggering intracellular signaling (cAMP, Ca2+) that leads to the exocytosis of GLP-1 and PYY [2, 4].