Glucagon-like peptide 1 secretion pathway (GLP-1 secretion pathway)

The Glucagon-like peptide 1 (GLP-1) secretion pathway is a complex physiological process primarily localized in the enteroendocrine L-cells of the distal small intestine and colon. This pathway is activated following nutrient ingestion, where carbohydrates, lipids, and bile acids are sensed by a variety of apical and basolateral receptors, including G protein-coupled receptors such as GPR40 (FFAR1), GPR119, and TGR5 (GPBAR1), as well as nutrient transporters like SGLT1 (Source: PubMed PMID 28107284, StatPearls NBK551568). Activation of these sensors leads to intracellular signaling cascades, typically involving increases in cyclic AMP or cytosolic calcium, which culminate in the exocytosis of GLP-1 into the portal circulation. Once released, GLP-1 acts as an incretin hormone, significantly enhancing glucose-dependent insulin secretion from pancreatic beta cells and inhibiting glucagon release from alpha cells, thereby maintaining euglycemia (Source: NIH/NIDDK). In patients with type 2 diabetes and obesity, the endogenous GLP-1 secretory response is often significantly blunted, contributing to postprandial hyperglycemia and impaired satiety (Source: PubMed PMID 15616790). Therapeutic strategies targeting this pathway aim to develop oral secretagogues that can restore or augment the natural release of GLP-1, offering a potentially more physiological approach to metabolic control compared to exogenous GLP-1 receptor agonists.

Other names

L-cell GLP-1 release pathwayIncretin secretion pathwayEndogenous GLP-1 secretion mechanism

Stimulation of enteroendocrine L-cells via nutrient-sensing receptors (e.g., GPR40, GPR119, TGR5) and metabolic pathways to trigger the exocytosis of endogenous GLP-1 (Source: PubMed PMID 24907567, 21917709).