GLP-1

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.

## Key PubMed References

[1] Holst JJ. "The physiology of glucagon-like peptide 1." Physiol Rev. 2007;87(4):1409-39. PMID: 17928588

[2] Drucker DJ. "The biology of incretin hormones." Cell Metab. 2006;3(3):153-65. PMID: 16517403

[3] Baggio LL, Drucker DJ. "Biology of incretins: GLP-1 and GIP." Gastroenterology. 2007;132(6):2131-57. PMID: 17498508

[4] Nauck MA, et al. "Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses." J Clin Endocrinol Metab. 1986;63(2):492-8. PMID: 3522621

[5] Muller TD, et al. "Glucagon-like peptide 1 (GLP-1)." Mol Metab. 2019;30:72-130. PMID: 31767182