Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-glucose–dependent mechanism.
Some incretins (GLP-1) also inhibit glucagon release from the alpha cells of the islets of Langerhans. In addition, they slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake. The two main candidate peptides that fulfill criteria for an incretin are the intestinal peptides glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP, also known as: glucose-dependent insulinotropic polypeptide). GIP is produced and secreted into the blood circulation by K cells, i.e., single cells located in the mucosa of the upper gastrointestinal tract's duodenum and upper jejunum while GLP1 is produced and secreted into the blood by L cells located in the mucosa of the lower gastrointestinal tracts small and large intestines. Short-chain fatty acids (primarily acetic, proprionic, and butyric acids), which microganisms form in the intestines, bind to the FFAR2 and FFAR3 receptors on K cells and L cells to stimulate their respective production and secretion of GIP and GLP-1. Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4) and are members of the glucagon peptide superfamily.
Several long-lasting GLP-1 analogs having insulinotropic activity have been developed, and several, including dulaglutide (Trulicity), exenatide (Byetta), liraglutide (Victoza), semaglutide (Ozempic, Wegovy and Rybelsus) and exenatide extended-release (Bydureon), have been approved for use in the U.S.
The incretin effect describes the phenomenon whereby oral glucose intake elicits a higher insulin response compared to intravenously introduced glucose that produces the same levels of serum glucose levels.
In 1932, Belgian physiologist Jean La Barre used the word "incretin" for a gut hormone, which stimulates the endocrine pancreas including insulin release. He also proposed that such incretins could be used as a treatment for diabetes mellitus.
- Nauck MA, Meier JJ (February 2018). "Incretin hormones: Their role in health and disease". Diabetes, Obesity & Metabolism. 20 Suppl 1: 5–21. doi:10.1111/dom.13129. PMID 29364588.
- Jorsal T, Rhee NA, Pedersen J, Wahlgren CD, Mortensen B, Jepsen SL, Jelsing J, Dalbøge LS, Vilmann P, Hassan H, Hendel JW, Poulsen SS, Holst JJ, Vilsbøll T, Knop FK (February 2018). "Enteroendocrine K and L cells in healthy and type 2 diabetic individuals". Diabetologia. 61 (2): 284–294. doi:10.1007/s00125-017-4450-9. PMID 28956082.
- Iwasaki K, Harada N, Sasaki K, Yamane S, Iida K, Suzuki K, Hamasaki A, Nasteska D, Shibue K, Joo E, Harada T, Hashimoto T, Asakawa Y, Hirasawa A, Inagaki N (March 2015). "Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion". Endocrinology. 156 (3): 837–46. doi:10.1210/en.2014-1653. hdl:2433/215430. PMID 25535828.
- Kim YA, Keogh JB, Clifton PM (June 2018). "Probiotics, prebiotics, synbiotics and insulin sensitivity". Nutrition Research Reviews. 31 (1): 35–51. doi:10.1017/S095442241700018X. PMID 29037268.
- Drucker DJ, Nauck MA (November 2006). "The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes". Lancet. 368 (9548): 1696–705. doi:10.1016/S0140-6736(06)69705-5. PMID 17098089. S2CID 25748028.
- Amori RE, Lau J, Pittas AG (July 2007). "Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis". JAMA. 298 (2): 194–206. doi:10.1001/jama.298.2.194. PMID 17622601.
- Rang HP, Ritter JM, Flower R, Henderson G (2016). Rang and Dale's Pharmacology (8th ed.). United Kingdom: Elsevier Churchill Livingstone. p. 385. ISBN 9780702053627. OCLC 903083639.
- Nauck, Michael A; Meier, Juris J (June 2016). "The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions". The Lancet Diabetes & Endocrinology. 4 (6): 525–536. doi:10.1016/s2213-8587(15)00482-9. ISSN 2213-8587. PMID 26876794.
- Rehfeld JF (2018-07-16). "The Origin and Understanding of the Incretin Concept". Frontiers in Endocrinology. 9: 387. doi:10.3389/fendo.2018.00387. PMC 6054964. PMID 30061863.