Glucagon-like peptide-1 (revision 6)
Old revision·16:16, 21 Jul 2024·EndpointEnid
| Glucagon-like peptide-1 | |
|---|---|
| Abbreviation | GLP-1 |
| Precursor | Proglucagon (gene GCG) |
| Principal source | Intestinal L cells |
| Topic infobox · conventions | |
Glucagon-like peptide-1 (GLP-1) is a 30- or 31-residue peptide hormone released from enteroendocrine L cells of the distal small intestine and colon in response to nutrient ingestion. It is one of the two principal incretin hormones, the other being Glucose-dependent insulinotropic polypeptide (GIP).[1]
GLP-1 is generated by tissue-specific post-translational processing of proglucagon, the same precursor that yields glucagon in pancreatic alpha cells. In the intestine, prohormone convertase 1/3 liberates GLP-1 (7–37) and its C-terminally amidated form GLP-1 (7–36) amide, the latter accounting for the majority of circulating immunoreactive GLP-1 in humans.[2]
Discovery and nomenclature
[edit]The existence of a gut-derived insulin secretagogue was inferred long before any such molecule was isolated: oral glucose was observed to provoke a substantially larger insulin response than an intravenous glucose load producing the same glycaemic excursion, a difference termed the incretin effect.[3]
Cloning of the proglucagon gene in the early 1980s revealed two glucagon-like sequences downstream of glucagon itself, designated glucagon-like peptide-1 and glucagon-like peptide-2. The full-length GLP-1 (1–37) proved to be biologically inert; N-terminal truncation to GLP-1 (7–37) yielded a potent insulinotropic peptide.[4] Physiological activity in humans was demonstrated shortly afterwards by infusion studies showing marked, glucose-dependent insulin release.[5]
Biosynthesis and secretion
[edit]Proglucagon is encoded by a single gene (GCG) and is processed differently in different tissues. In pancreatic alpha cells, prohormone convertase 2 predominates and glucagon is the principal product. In intestinal L cells and in some neurons of the caudal brainstem, prohormone convertase 1/3 predominates and the products are GLP-1, GLP-2 and the glicentin-related fragments.[2]
L cells are open-type epithelial cells whose apical surface contacts the lumen, giving them direct access to nutrient stimuli. Secretion is biphasic: an early rise within 10–15 minutes of ingestion, attributed partly to neural and endocrine relay from the proximal gut, followed by a later phase as nutrients reach the ileum and colon.[1]
References
- ^ a b Holst JJ. "The physiology of glucagon-like peptide 1." Physiological Reviews 87(4):1409–1439 (2007). DOI:10.1152/physrev.00034.2006. PMID 17928588.
- ^ a b Baggio LL, Drucker DJ. "Biology of incretins: GLP-1 and GIP." Gastroenterology 132(6):2131–2157 (2007). DOI:10.1053/j.gastro.2007.03.054. PMID 17498508.
- ^ Nauck M, Stöckmann F, Ebert R, Creutzfeldt W. "Reduced incretin effect in type 2 (non-insulin-dependent) diabetes." Diabetologia 29(1):46–52 (1986). PMID 3514343.
- ^ Holst JJ, Ørskov C, Nielsen OV, Schwartz TW. "Truncated glucagon-like peptide I, an insulin-releasing hormone from the distal gut." FEBS Letters 211(2):169–174 (1987). PMID 3542566.
- ^ Kreymann B, Williams G, Ghatei MA, Bloom SR. "Glucagon-like peptide-1 7–36: a physiological incretin in man." The Lancet 2(8571):1300–1304 (1987). PMID 2890903.