Glossary
GLP-1
GLP-1 is an incretin hormone from the gut whose native half-life is only ~2 minutes. How it works, why DPP-4 cuts it, and why analogs lead metabolic research.
Glucagon-like peptide-1 (GLP-1) belongs to the incretin hormones and is secreted by L-cells in the intestine after a meal. It is generated when proglucagon is processed in a tissue-dependent way — the precursor that pancreatic alpha-cells turn into glucagon — and its main circulating active species are GLP-1(7-37) and the amidated GLP-1(7-36).
What the literature describes
Its target, the GLP-1 receptor, is a class B GPCR present on pancreatic beta-cells and also in vagal afferents, the heart, the hypothalamus and the brainstem. Binding increases intracellular cAMP; animal and human studies report glucose-dependent insulin release, lower glucagon secretion, delayed gastric emptying and decreased food intake. In plasma, native GLP-1 lasts only about two minutes, because DPP-4 cuts it after the second residue and the kidneys clear what is left.
Why analogs were needed
That very short half-life is precisely why engineered analogs were developed. An Aib at position 8 stops DPP-4, and a fatty-acid acyl chain encourages albumin binding; together they stretch the duration of action from minutes into days. Both semaglutide and liraglutide were engineered this way as GLP-1 receptor agonists.
Related terms
incretin · GIP · glucagon receptor · half-life. Browse GLP-1 and incretin peptides, the GLP-1 research family, or Semaglutide.