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GLP-1
The naturally occurring incretin hormone that regulates blood sugar and appetite, serving as the biological template for the revolutionary GLP-1 receptor agonist drug class.
Overview
GLP-1 (Glucagon-Like Peptide-1) is a 30-amino acid incretin hormone produced by intestinal L-cells in response to food intake. It is one of two primary incretin hormones responsible for the observation that oral glucose produces a greater insulin response than intravenous glucose at the same blood level. GLP-1 has profound effects on glucose metabolism, appetite, and gastrointestinal function.
GLP-1 stimulates insulin secretion and suppresses glucagon in a glucose-dependent manner, reducing hypoglycemia risk. It also slows gastric emptying, contributing to satiety. However, native GLP-1 has an extremely short half-life of 1-2 minutes due to rapid DPP-4 enzyme cleavage, making it impractical as a therapeutic agent.
This limitation led to two strategies: DPP-4 inhibitors that slow GLP-1 breakdown, and GLP-1 receptor agonists modified to resist DPP-4. The latter approach produced the most impactful drug class in modern obesity and diabetes treatment. GLP-1 receptors exist in the brain, heart, kidneys, and other organs, suggesting effects beyond glucose regulation.
Central nervous system GLP-1 signaling plays roles in appetite regulation, reward pathways, and possibly neuroprotection. Understanding of GLP-1 biology forms the foundation for the entire GLP-1 agonist drug class that has transformed diabetes and obesity treatment globally.