Glucagon-like peptide-1GLP-1
The incretin that anchors the modern metabolic toolkit.
Identity
- Class
- Proglucagon-derived peptide (~30–31 aa)
- Source
- Intestinal L-cells (and some CNS neurons)
- Receptor
- GLP-1 receptor (GLP-1R), a class B GPCR
Key properties
Molecular weight
~3,297.7 Da
Approximate values for the native hormone. Engineered analogs are often deliberately larger and far longer-acting.
Mechanism
Released from gut L-cells in response to nutrients, GLP-1 binds GLP-1R on pancreatic beta cells to amplify glucose-dependent insulin secretion. It also slows gastric emptying and signals satiety centrally. Native GLP-1 is degraded within minutes by DPP-4, which is why long-acting receptor agonists are engineered for protease resistance.
Reference notes
- Glucose-dependence is the safety crux: GLP-1 augments insulin only when glucose is elevated, limiting hypoglycemia risk relative to insulin secretagogues.
- Co-agonism with GIP (and, in some candidates, glucagon) is an active design strategy aimed at additive metabolic effects.
- The very short native half-life is the central pharmacological problem its agonists are built to solve.
Selected literature
Curated peer-reviewed reviews, sourced from PubMed. Selected for relevance, not exhaustive — open any entry on PubMed for the full record and its primary citations.
- 1.Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1 · Cell metabolism, 2018 · PMID 29617641
- 2.The physiology of glucagon-like peptide 1 · Physiological reviews, 2007 · PMID 17928588
- 3.Glucagon-like peptide-1 receptor: mechanisms and advances in therapy · Signal transduction and targeted therapy, 2024 · PMID 39289339