Is GLP-1 a Hormone?
Yes, GLP-1 (Glucagon-Like Peptide-1) is definitively an endogenous incretin hormone produced by L-cells in the intestinal mucosa in response to nutrient intake. 1
Hormonal Classification and Origin
GLP-1 is an incretin hormone secreted by enteroendocrine L-cells located in the terminal ileum and proximal colon following ingestion of nutrients, particularly glucose and triglycerides 1, 2
The hormone is also produced by islet cells in the pancreas and neurons in the nucleus tractus solitarius in the brainstem 1
GLP-1 is encoded in the proglucagon gene and represents a proglucagon cleavage product 1, 3
Endogenous GLP-1(7-37) represents less than 20% of total circulating endogenous GLP-1 and has an extremely short half-life of approximately 1.5-2 minutes due to rapid degradation by dipeptidyl peptidase-4 (DPP-IV) and neutral endopeptidases 4, 1
Physiological Hormonal Actions
GLP-1 functions as a hormone through multiple receptor-mediated mechanisms:
Pancreatic effects: Stimulates glucose-dependent insulin secretion from pancreatic β-cells and suppresses glucagon secretion from α-cells 5, 4, 2
Gastrointestinal effects: Delays gastric emptying and inhibits gastric acid secretion 5, 3
Central nervous system effects: Promotes satiety and reduces food intake through hypothalamic pathways 1, 2
Metabolic integration: The combined actions result in reduction of circulating glucose concentrations 3
Receptor Distribution
GLP-1 exerts its hormonal effects by binding to GLP-1 receptors, which are seven-transmembrane domain G-protein-coupled receptors expressed in multiple organs 4, 3
Receptors are found in the pancreas, gastrointestinal tract, heart, brain, kidney, lung, and thyroid, demonstrating the hormone's pleiotropic physiological effects 1
Receptor activation leads to increased intracellular cyclic AMP (cAMP) and calcium mobilization, triggering downstream hormonal signaling cascades 4, 3
Clinical Context
The "incretin effect"—where oral glucose produces greater insulin secretion than intravenous glucose—is mediated by GLP-1 and contributes to two-thirds of total insulin secretion in response to oral glucose loads 1
This incretin effect is characteristically blunted in type 2 diabetes mellitus, highlighting GLP-1's role as a critical metabolic hormone 1, 6
Impaired GLP-1 secretion observed in type 2 diabetes suggests the hormone plays a pathogenic role in this disorder 2